Skip to main content
Download PDF
Download ePub

Novel ecofriendly spectrophotometric methods for the determination of six dihydropyridines calcium channel blockers through derivatization with sulfophtalein dye: application to tablet analysis

BMC Chemistry volume 19, Article number: 8 (2025) Cite this article

Abstract

Novel, «green» and simple visible spectrophotometric procedures for the determination of six dihydropyridines CCBs (amlodipine besylate (AML), lacidipine (LAC), levamlodipine besylate (LAML), nifedipine (NIF), nimodipine (NIM) and nitrendipine (NIT)) through derivatization with the sulfophthalein dye bromophenol blue (BPB) have been developed. The optimal parameters for CCBs spectrophotometric analysis via complex formation using BPB were as follows: detection wavelength—596 nm, reaction time—5 min, ratio of reacting components—1:1, operating temperature—25 ± 2 °C. The concentration was linearly proportional to absorbance values in the range of 3.40—17.00 μg/mL (AML), 1.14—9.11 μg/mL (LAC), 1.14—9.08 μg/mL (LAML), 4.16—12.40 μg/mL (NIF), 0.84—5.86 μg/mL (NIM), 6.52—19.60 μg/mL (NIT). The developed methods are colorimetric and therefore does not require a UV instrument to quantify these drugs. The proposed approach was more efficient in terms of time reliability, sensitivity and «greenness» than other recorded spectrophotometric methods and can be easily implemented for routine pharmaceutical analysis.

Peer Review reports

Introduction

According to the last data analysis of the World Health Organization, hypertension has a leading position in cases causing death. Approximately 1.35 billion of individuals in the world suffer from hypertension [1]. Various antihypertension classes, including diuretics, α- and β-blockers, angiotensin converting enzyme (ACE) inhibitors, and calcium channel blockers (CCB), are widely prescribed all over the world. Plenty of people with high blood pressure (HBP) require treatment that is absolutely available, safe, and effective for their needs [2]. CCB are a category of medicines mostly used to treat hypertension (Fig. 1). These drugs are also helpful in other pathological states. CCBs are classified into two classes based on their formula and duration: dihydropyridine and non-dihydropyridine. Besides that, dihydropyridines exist in four generations [3,4,5,6,7,8,9,10,11,12,13,14,15,16].

Fig. 1
figure 1

Chemical structure of the discussed dihydropyridine CCBs. Amlodipine (AML), Lacidipine (LAC), Levamlodipine (LAML), Nifedipine (NIF), Nimodipine (NIM), Nitrendipine (NIT)

Full size image

High-performance liquid chromatography (HPLC) and redox titration methods have been presented in the monographs of Pharmacopeias for the assay of various CCBs in bulk and dosage form [17, 18]. Plenty of available literature reviews have been revealed regarding chromatographic and tandem spectrometry procedures, for instance, HPLC or reverse phase HPLC determination of CCBs in tablets and human plasma [19, 20]. Liquid chromatography mass spectrometry procedures for bioavailability and chiral conversion were preferred [21, 22]. Alternative approaches, including rapid capillary electrophoresis for the determination of enantiomeric contaminants [23], molecular docking [24] and investigation of binding characteristics, were described [25]. Even though these approaches are extremely helpful, specific, and sensitive, most of them were require critical conditions such as costly, time-consuming, laborious, and professional operation. Considering the simplicity, cheapness, low reagent consumption, availability in the most quality control laboratories and greenness of spectrophotometric techniques, quite a few procedures have been highlighted in the literature sources for the analysis of CCBs in bulk, pharmaceutical forms and biological fluids [26, 27]. A number of UV-spectrometric measurements have been performed in different polar and non-polar solvents for the discussed CCBs [28,29,30,31]. Micelle enhanced spectrofluorimetric determination of some CCBs was also reported [32]. For increasing specificity, some authors proposed interactions between the analyzed CCBs and some reagents, which are presented in Table 1. Most of the presented procedures have limitation (involve reducing of the analyzed CCBs, heating, damaging reagents, or acidic or alkaline mediums) that are negative for modern application of technique. Sulfophthalein dyes are commonly used as indicators in acid–base titrations. It was considered that these molecules colored and absorbed visible light. According to the authors [51], dyes were defined as old, but gold. For the spectrophotometric determination some CCBs, varieties of dyes have been used, such as bromophenol blue (BPB), bromothymol blue (BTB), bromocresol green (BCG) etc. It is worth noting, that proposed procedures contain pros and cons, which are illustrated in Table 2. The most commonly analyzed spectrophotometric procedures for assay CCBs with dyes had a lack of disadvantages that included extraction, pH adjustment, non-ecofriendly reagents, etc.

Table 1 Spectrophotometric determination of some CCBs with utilized reagents
Full size table
Table 2 Spectrophotometric determination of some CCBs with dyes
Full size table

The present paper represents a novel, «green» and simple visible spectrophotometric procedure for the determination of six dihydropyridines CCBs based on their interaction with the sulfophthalein dye bromophenol blue (BPB).

Experimental

Instrumentation

As analytical devices Shimadzu UV-1800 double beam UV–vis spectrophotometer (Japan) with attached UV-Probe version 2.70 software was employed to perform spectrophotometric measurements. RAD WAG AS 200/C precise analytical balance (Poland) and ultrasonic bath Elmasonic EASY 60H (Germany) with 100% ultrasonic power at a frequency of 40 kHz were utilized in the developed procedure.

Reagents and standards

Amlodipine besylate (AML), lacidipine (LAC), levamlodipine besylate (LAML), nifedipine (NIF), nimodipine (NIM) and nitrendipine (NIT) (purity ≥ 98% (HPLC)) were supplied from Sigma-Aldrich Chemicals Co. (St. Louis, MO, USA).

Amlodipine besylate 10 mg tablets («Amlodipine» Farmak), Nitrendipine 10 mg tablets («Nitresan» PRO. MED. CS Praha a. s.), Nifedipine 20 mg tablets («Nifedipine» Lekhim), Levamlodipine besylate 5 mg tablets («Semlopin» Kusum Pharm), Nimodipine 30 mg tablets («Nimodipine» PJSC SIC “Borshchahivskiy CPP”) were purchased from local drugstore. Lacidipine 2 mg tablets (“Lacipil” GlaxoSmithKline) was purchased from europharm.com.ua.

All used in these studies solvents including methanol, ethanol, chloroform, acetonitrile and ethyl acetate were produced by Honeywell and had a purity of 99.9%. BPB were acquired from Sigma-Aldrich Chemicals Co. (USA, St. Louis). All chemicals utilized in the experiment were analytical grade.

Standard analytical procedure

Preparation of BPB solution for determination of AML and NIF

A 6.0 × 10–4 M of BPB was prepared in a 50.00 mL measuring flask by dissolving 20.76 mg of BPB in 40 mL of methanol and adjusting to the mark with the same solvent.

Preparation of BPB solution for determination of NIT

A 9.0 × 10–4 M of BPB was prepared in a 25.00 mL measuring flask by dissolving 15.6 mg of BPB in 20 mL of methanol and adjusting to the mark with the same solvent.

Preparation of BPB solution for determination of LAML and LAC

A 1.0 × 10–3 M of BPB was prepared in a 25.00 mL measuring flask by dissolving 16.8 mg of BPB in 20 mL of methanol and adjusting to the mark with the same solvent.

Preparation of BPB solution solution for determination of NIM

A 1.0 × 10–3 M of BPB was prepared in a 25.00 mL measuring flask by dissolving 16.8 mg of BPB in 20 mL of acetonitrile and adjusting to the mark with the same solvent.

Preparation of standard solution

Standard stock solutions were prepared by dissolving 25 mg in 15 ml of solvent (methanol for AML, NIF, NIT, LAML/acetonitrile for NIM, LAC), followed by dilution to a final volume in 25 ml vessels, then diluted with suitable solvents to obtain a concentrations 3.40—17.00 µg/mL for AML, 4.16—12.40 µg/mL for NIF, 6.52—19.60 µg/mL for NIT, 1.13—9.08 µg/mL for LAML, 0.84—5.86 µg/mL for NIM, 1.14—9.11 µg/mL for LAC.

Calibration curve construction

Standard stock solutions were transferred to a series of 10 mL volumetric flasks. The volume transferred varied to achieve the desired concentration ranges: (0.1–0.5 mL) for AML, (0.2–0.6 mL) for NIF, (0.2–0.6 mL) for NIT, (0.1–0.8 mL) for LAML, (0.2–1.4 mL) for NIM and (0.05–0.4 mL) for LAC. These concentration ranges allowed for the concentration ranges of 3.40 – 17.00 µg/mL for AML, 4.16 – 12.40 µg/mL for NIF, 6.52 – 19.60 µg/mL for NIT, 1.13 – 9.08 µg/mL for LAML, 0.84 – 5.86 µg/mL for NIM, 1.14 – 9.11 µg/mL for LAC, respectively. The solutions were analyzed by adding BPB 1.0 mL of 6.0 × 10–4 M for AML, NIF, NIT, LAC and 0.3 mL of 1.0 × 10–3 M for LAML, NIM and making up to the mark by solvent. The absorbance of the resulting mixtures were registered at 596 nm against a reference solutions prepared in the same way without adding the analyte.

Application to tablet analysis

Twenty tablets of AML, LAC, LAML, NIF, NIM and NIT were thoroughly crushed and weighed. Sample preparation was carried out as described in Sect. "Preparation of Standard solution" with filtration using a Whatman No. 42 filtering paper.

Results and discussion

Methodology for choosing a reagent for the development of spectrophotometric methods for the determination of dihydropyridines CCBs

The use of sulfophthalein dyes is quite promising in the modern spectrophotometric analysis of drugs. The advantages of consuming these reagents are environmental friendliness, short sample preparation, speed and cost of analysis. Sulfophthalein dyes belong to the acid-basic group and can interact in solution in the form of two tautomeric (hydrogenated) forms, the first- monoanionic, which forms a yellow quinoid structure upon interaction in which the analyte splits off a proton (in the cause of BPB), and the second—dianionic is a blue-colored sulfophthalein decomposition product due to the loss the analyte of one more proton [59]. After reviewing scientific sources, it was established that some of dihydropyridines CCBs have already been studied using sulfophthalein dyes (Table 2) however almost all of them used chloroform extraction and heating, which negatively affects not only sample preparation, increasing the duration of the analysis, but also safety and environmental friendliness. Therefore, our task in the course of preliminary experimental studies was to select the optimal reagent for the development of the spectrophotometric methods for the determination of AML, LAC, LAML, NIF, NIM and NIT in dosage forms without using extraction and heating. To select an effective reagent for the development of the spectrophotometric procedure for the determination of dihydropyridines CCBs were tested a number of sulfophthalein dyes: BPB, BCG, BTB, bromocresol purple (BCP), thymol blue (TB), cresol red (CR) and phenol red (PR) (Table 3). We were not interested in the UV part of the spectrum, therefore, in some figures are observed the truncated absorption maxima of the reaction products.

Table 3 Methodology for choosing a reagent for the development of the spectrophotometric methods for the determination of dihydropyridines CCBs
Full size table

Methodology for choosing a reagent for the development of the spectrophotometric methods for the determination of AML in dosage forms.

In order to select the optimal reagent for the development of the spectrophotometric method for the determination of AML in dosage forms were tested BCG, BTB, BPB, BCP, PR, CR, TB. Fig. S. 3.1.1 (Appendix A) shows the absorbance spectra obtained during the approbation of BCG as a potential reagent for the spectrophotometric procedure of the determination of AML. As can be seen from Fig. S. 3.1.1 (Appendix A), BCG and AML interact and form a product with an absorbance maximum at a wavelength of 350 nm. Methanol was chosen as the optimal solvent. For further method development the necessary was pH correction, which complicate sample preparation and negatively affect the "greenness" of the method. Fig. S. 3.1.2 (Appendix A) illustrated the absorbance spectra obtained when BTB was used as a potential reagent for the spectrophotometric method of the determination of AML. As can be seen from Fig. S. 3.1.2 (Appendix A) a shift of the formed complex with a maximum at a wavelength of 350 nm was observed, while the complex and BTB against acetonitrile was registered at 405 nm. The obtained results required a change of pH, as with the previous BCG reagent. The next dye that we tested for the development of the spectrophotometric method for the determination of AML was BPB. As a result of the interaction of AML with BPB was formed a reaction product with an absorbance maximum at a wavelength of 596 nm. Adding AML to the BPB solution decreases the absorbance band of the monoionized dye form while increases the absorbance band of the doubly ionized form. Absorbance spectra of the reaction product of AML with BPB are presented in Fig. S. 3.1.3 (Appendix A). Considering the results received in Fig. S. 3.1.3, we were interested in BPB as a reagent for the further method development. Fig. S. 3.1.4 (Appendix A) demonstrated the absorbance spectra obtained during the approbation of BCP as a potential reagent for the development of a spectrophotometric procedure for the determination of AML. Ethyl acetate was chosen as the optimal solvent. As can be seen from Fig. S. 3.1.4 (Appendix A), the interaction of BCP and AML produced a product with an absorbance maximum at a wavelength of 370 nm, however, similarly to the previous dyes BCG and BTB need to adjust the pH, which was inappropriate for routine drug analysis. Fig. S. 3.1.5 (Appendix A) illustrates the absorbance spectra of the reaction product of AML with the next tested sulfophthalein dye—PR. The achived results from Fig. S. 3.1.5 (Appendix A) indicate that AML does not interact with PR however the absorbance of the dye was greater than that of the complex against acetonitrile. Fig. S. 3.1.6 (Appendix A) shows the absorbance spectra obtained when testing CR as a potential reagent for the determination of AML. Similarly, as with BCG, BTB, BCP, further development of the methodology required the pH adjustment, which complicates sample preparation. The last tested sulfophthalein dye as a potential reagent for the development of the spectrophotometric method for the determination of AML was TB. The absorbance spectra of the reaction product in acetonitrile are shown in Fig. S. 3.1.7 (Appendix A). It turned out to be interesting that TB interacted better with AML in a methanol–acetonitrile solution. As can be seen from Fig. S. 3.1.8 (Appendix A), the maximum absorbance of the product of the interaction of AML with TB in the methanol–acetonitrile medium was observed at a wavelength of 370 nm, while in acetonitrile (Fig. S. 3.1.7 (Appendix A)) at 350 nm. The solvatochromic effect of organic solvents leads to a shift in the position of these forms. However, in subsequent studies, problems arose with the linearity of the analytical method, which may be related to the need to adjust the pH. Therefore, from all the above-mentioned sulfophthalein dyes, BPB was chosen for the method further development of AML in dosage forms.

Methodology for choosing a reagent for the development of the spectrophotometric methods for the determination of NIF in dosage forms

In order to select the optimal reagent for the development of the spectrophotometric method for the determination of NIF in dosage forms were tested BCG, BTB, BPB, BCP, PR, CR. Fig. S. 3.2.1 (Appendix B) shows the absorbance spectra obtained during the approbation of BCG as a potential reagent for the spectrophotometric method of determining NIF. As shown in Fig. S. 3.2.1 (Appendix B), BCG interacts with NIF and forms a product with an absorbance maximum at a wavelength of 350 nm. Methanol was chosen as the optimal solvent. However, it was necessary for the further method development to adjust the pH, which leads to the complication of sample preparation and negatively affect the "greenness" of the method. Fig. S. 3.2.2 (Appendix B) demonstrated the absorbance spectra obtained when BTB were used as a potential reagent for the spectrophotometric procedure of the determination NIF. As can be seen from Fig. S. 3.2.2 (Appendix B), the formation of the reaction product of NIF and BTB was not observed, so it could be concluded that NIF did not interact with BTB. Absorbance spectra of the reaction product of NIF and potential reagent BPB presented in Fig. S. 3.2.3 (Appendix B). NIF interacts with BPB with formation of a complex with an absorbance maximum at a wavelength of 596 nm. Adding NIF to the BPB solution decreases the absorbance band of the monoionized dye form while increases the absorbance band of the doubly ionized form. Considering the results obtained in Fig. S. 3.2.3 (Appendix B), we were interested in BPB as a reagent for the further method development. Fig. S. 3.2.4 (Appendix B) shows the absorbance spectra obtained when BCP was tested as a potential reagent for the method development. Ethyl acetate was chosen as the optimal solvent. As can be seen from Fig. S. 3.2.4 (Appendix B), BCP did not react with NIF, similarly to BTB. Fig. S. 3.2.5 (Appendix B) illustrated the absorbance spectra obtained during the approbation of PR as a potential reagent for the development of the spectrophotometric procedure for the determination of NIF. As can be seen from Fig. S. 3.2.5 (Appendix B), NIF did not interact with PR, the same conclusion as for previously tested reagents BTB, BCP. Fig. S. 3.2.6 (Appendix B) shows the absorbance spectra obtained when testing CR as a potential reagent for the determination of NIF. As can be seen from Fig. S. 3.2.6 (Appendix B), the further development of the method involves adjusting the pH, which increases the duration of the analysis and affect the «greeness» of the method. From the above mentioned, it can be concluded that among all tested sulfophthalein dyes, BPB was chosen as a potential reagent for the development of the spectrophotometric method for the determination of NIF in dosage forms.

Methodology for choosing a reagent for the development of spectrophotometric methods for the determination of NIT in dosage forms

In order to select the optimal reagent for the development of the spectrophotometric method for the determination of NIT in dosage forms were tested BCG, BTB, BPB, BCP, CR, TB. Fig. S. 3.3.1 (Appendix C) shows the absorbance spectra obtained during the approbation of BCG as a potential reagent for the spectrophotometric method of determining NIT. As shown in Fig. S. 3.3.1 (Appendix C), BCG interacts with NIT and forms a product with an absorbance maximum at a wavelength of 350 nm. Methanol was chosen as the optimal solvent. However, it was necessary for the further development of the method to adjust the pH, which leads to the complication of sample preparation and negatively affect the "greenness" of the analytical method. Fig. S. 3.3.2 (Appendix C) illustrated the absorbance spectra obtained during the approbation of BTB as a potential reagent for the spectrophotometric method of determination NIT. As can be seen from Fig. S. 3.3.2 (Appendix C), the formation of the product of the reaction of NIT and BTB was observed. However, for further method development required the adjustement the pH, similarly to BCG. Absorbance spectra of the reaction product of NIT when testing a potential reagent BPB are presented in Fig. S. 3.3.3 (Appendix C). NIT interacts with BPB with formation of the reaction product with an absorbance maximum at a wavelength of 596 nm. Adding NIT to the BPB solution decreases the absorbance band of the monoionized dye form while increases the absorbance band of the doubly ionized form. Considering the results obtained in Fig. S. 3.3.3 (Appendix C), we were interested in BPB as a reagent for the further method development. Fig. S. 3.3.4 (Appendix C) shows the absorbance spectra obtained during the approbation of BCP as a potential reagent for the development of a method for the spectrophotometric determination of NIT. Ethyl acetate was chosen as the optimal solvent. As can be seen from Fig. S. 3.3.4 (Appendix C), BCP did not react with NIT. Fig. S. 3.3.5 (Appendix C) illustrates absorbance spectra obtained using CR as a potential reagent for the determination of NIT. As can be seen from Fig. S. 3.3.5 (Appendix C), the further method development involves adjusting the pH, which leads to an increase in the duration of the analysis and will affect environmental friendliness methods, the same conclusion as for previously tested BCG and BTB dyes. The last tested sulfophthalein dye as a potential reagent for the development of the spectrophotometric method for the determination of NIT was TB. The absorbance spectra of the reaction product in acetonitrile are shown in Fig. S. 3.3.6 (Appendix C). NIT did not interact with TB, similarly to BCP. So, from all tested sulfophthalein dyes, BPB was chosen as a potential reagent for the development of the spectrophotometric method for the determination of NIT in dosage forms.

Methodology for choosing a reagent for the development of the spectrophotometric methods for the determination of NIM in dosage forms

In order to choose the optimal reagent for the development of the spectrophotometric method for the determination of NIM in dosage forms were tested BTB, BPB, BCP, CR, TB. Fig. S. 3.4.1 (Appendix D) presented absorpbance spectra obtained during the testing of BTB as a potential reagent for the development of the spectrophotometric method for the determination of NIM. As can be seen from Fig. S. 3.4.1 (Appendix D), NIM interacts with BTB however this technique requires pH adjustment, which negatively affects the aspects described above. Fig. S. 3.4.2 (Appendix D) shows the absorbance spectra obtained during the testing of BCP as a potential reagent for the development of a method for the determination of NIM. Methanol was chosen as the optimal solvent. As can be seen from Fig. S. 3.4.2 (Appendix D), a high value of the absorbance was observed in the spectra. Since BCP did not interact with NIM, we did not dilute the solutions to obtain a satisfactory value of the absorbance. Fig. S. 3.4.3 (Appendix D) shows the absorbance spectra obtained during the approbation of CR as a potential reagent for the method development. As can be seen from Fig. S. 3.4.3 (Appendix D), NIM interacts with CR however requires pH adjustment, like previously tested BTB. The absorpbance spectra of the reaction product of NIM with TB in acetonitrile are shown in Fig. S. 3.4.4 (Appendix D). NIM interacts with TB however further development of the method requires changing the pH of the medium, the same conclusion as for previously tested dyes BTB and CR. Therefore, among the above-mentioned sulfophthalein dyes, BPB Fig. S. 3.4.5 (Appendix D) was a potential reagent for the development of the spectrophotometric method for the determination of NIM in dosage forms.

Methodology for choosing a reagent for the development of the spectrophotometric methods for the determination of LAC in dosage forms

Taking into consideration the bank of negative results obtained during the investigation of the previous four analytes with sulfophthalein dyes, we decided that it is impractical to conduct further studies with the consumption of a large number of solvents, test substances and dyes. While next developing the further methodology for the selection of reagents, we changed the methodology and approach to the selection of reagents and began to use the « plate method», which significantly saved our time. A visual method was proposed for assessing the interaction of the analyte with the dye using a plate. Fig. S. 3.5.1 (Appendix E) shows a plate with experimental data on the interaction of LAC and sulfophthalein dyes, as potential reagents (TB, methyl red (MR), CR, PR, BCP, BCG, BPB, BTB). A blank solution was added to columns 1, 3, and 5, which consisted of 1 drop of dye solution + 1 drop of methanol + 13 drops of solvent (1-MetOH, 3-EtOH, 5-ACN). In columns 2, 4 and 6 were added the test solution, which consisted of 1 drop of dye solution + 1 drop of LAC solution + 13 drops of solvent (1-MetOH, 3-EtOH, 5-ACN). As can be seen from Fig. S. 3.5.1 (Appendix E), the color change in compartment G indicates the formation of a complex of LAC with BPB. All other tested dyes did not interact with LAC under normal conditions, since the color of the blank solution did not differ from the complex or was more intense.

Methodology for choosing a reagent for the development of the spectrophotometric methods for the determination of LAML in dosage forms

A visual method was proposed of choosing a potential reagent for the development of a spectrophotometric method for the determination of LAML in dosage forms using a plate. Fig. S. 3.6.1 (Appendix F) shows a plate with experimental data on the interaction of LAML and sulfophthalein dyes, as potential reagents (TB, MR, CR, PR, BCP, BCG, BPB, BTB). A blank solution was added to columns 1, 3, and 5, which consisted of 1 drop of dye solution + 1 drop of methanol + 13 drops of solvent (1-MetOH, 3-EtOH, 5-ACN). In columns 2, 4 and 6 were added the test solution, which consisted of 1 drop of dye solution + 1 drop of LAML solution + 13 drops of solvent (1-MetOH, 3-EtOH, 5-ACN). As can be seen from Fig. S. 3.6.1 (Appendix F), the color change in compartment G indicates the formation of a complex of LAML with BPB. All other tested dyes did not interact with LAML under normal conditions, since the color of the blank solution did not differ from the complex or was more intense.

Selection the optimal conditions for the development of the spectrophotometric methods for the determination of dihydropyridines CCBs

As it was mentioned in Sect. 3.1, the spectrophotometric determination based on ion pair formation are among the most important optical instrumental quantitative methods and warrant special attention due to their prominent application in drug quantification. Sulfophthaleins are one of the most interesting dye families in the development of such techniques and they have drawn scientific interest because of their molecular structure, which enables the formation of ion-pair complexes with a variety of drugs and their anionic nature even at acidic pH due to the presence of a sulfonic group in its dissociated form [59]. It was shown that some CCBs drugs can be spectrophotometrically determined using BPB as for ion-pair complexes formation [54, 55]. Scientific publications [54, 55] describe the methods for the determination of AML and NIF using BPB however the use of chloroform as a toxic solvent and an analytical wavelength of 413–415 nm (monoanionic form) were required, which indicated the outdated approaches in the development of methods due to the time of development of methods (2004, 2010). BPB is a dye that has been used as an industrial dye, a laboratory indicator and a biological stain. BPB is not a hazardous substance and can be used as reagent for «green» analysis. It has a role as a two-colour indicator, an acid–base indicator, changing from yellow below pH 3 to purple at pH 4.6 [60]. The absorbance spectra of the BPB complex with several CCBs, such as AML, LAC, LAML, NIF, NIM and NIT, are displayed in Figs. 2, 3, 4, 5, 6, 7. The absorbance maxima of these drugs were located at 596 nm.

Fig. 2
figure 2

Absorbance spectra of AML, BPB and AML—BPB complex vs. appropriate solvent (c(BPB) = 6.00 × 10–5 M, c(AML) = 1.80 × 10–5 M)

Full size image
Fig. 3
figure 3

Absorbance spectra of LAC, BPB and LAC—BPB complex vs. appropriate solvent (c(BPB) = 3.00 × 10–5 M, c(LAC) = 1.00 × 10–5 M)

Full size image
Fig. 4
figure 4

Absorbance spectra of LAML, BPB and LAML—BPB complex vs. appropriate solvent (c(BPB) = 3.00 × 10–5 M, c(LAML) = 1.40 × 10–5 M)

Full size image
Fig. 5
figure 5

Absorbance spectra of NIF, BPB and NIF—BPB complex vs. appropriate solvent (c(BPB) = 6.00 × 10–5 M, c(NIF) = 2.40 × 10.5 M)

Full size image
Fig. 6
figure 6

Absorbance spectra of NIM, BPB and NIM—BPB complex vs. appropriate solvent (c(BPB) = 3.00 × 10–5 M, c(NIM) = 1.00 × 10–5 M)

Full size image
Fig. 7
figure 7

Absorbance spectra of NIT, BPB and NIT—BPB complex vs. appropriate solvent (c(BPB) = 9.02 × 10–5 M, c(NIT) = 3.64 × 10–5 M)

Full size image

This approach was important as it avoids the need for an extraction step, which was the primary motivation behind developing this analytical procedure. Some experimental settings for the reaction must be tuned in order to establish the optimal spectrophotometric conditions for the analysis of CCBs drugs using reaction with BPB. Correct selection of organic solvents was crucial as it facilitates and guarantees the interaction between the analyte and BPB, resulting in the production of the appropriate colored product. For the purpose of comparing solvents, acetonitrile, chloroform, methanol,ethanol and ethyl acetate were used. The solvent selection results are shown in Fig. 8. For AML, LAML, NIF and NIT methanol was considered the optimal solvent, whereas for NIM it was acetonitrile. LAC-BPB complex achieves the highest absorbance in ethylacetate however the solution was stable for less than 5 min, so we recommended acetonitrile as a solvent for LAC determination too. The influence of dye concentration on the absorption increasing of its complex with LAC at the selected analytical wavelength was studied. It was demonstrated that the optimal BPB concentration was 3.00 × 10–5 M (Fig. S 3.7.1 (Appendix G)). When methanol was present in the reaction mixture during LAC determination, absorption increases. The ideal concentration of methanol was found to be 8% (Fig. S 3.7.2 (Appendix G)).

Fig. 8
figure 8

Effects of solvents on CCBs drugs—BPB complex formation (AML (c(BPB) = 6.00 × 10–5 M, c(AML) = 1.80 × 10–5 M), LAC (c(BPB) = 5.00 × 10–5 M, c(LAC) = 2.50 × 10–5 M), LAML (c(BPB) = 2.00 × 10–5 M, c(LAML) = 2.00 × 10–6 M), NIF (c(BPB) = 6.00 × 10–5 M, c(NIF) = 2.40 × 10–5 M), NIM (c(BPB) = 3.00 × 10–5 M, c(NIM) = 2.00 × 10–6 M), NIT (c(BPB) = 3.64 × 10–5 M, c(NIT) = 9.02 × 10–5 M)

Full size image

The stability of the analyzed CCBs and BPB ion-pair complexes was examined. The mixture was kept at a constant temperature of 25 ± 2 °C for at least five minutes and remained stable for at least an hour, even though the ion pairs formed immediately (Fig. 9).

Fig. 9
figure 9

Stability of some CCBs drugs complexes with BPB in time (AML (c(BPB) = 6.00 × 10–5 M, c(AML) = 2.40 × 10–5 M), LAC (c(BPB) = 3.00 × 10–5 M, c(LAC) = 1.00 × 10–5 M), LAML (c(BPB) = 3.00 × 10–5 M, c(LAML) = 1.40 × 10–5 M), NIF (c(BPB) = 6.00 × 10–5 M, c(NIF) = 6.00 × 10–5 M), NIM (c(BPB) = 3.00 × 10–5 M, c(NIM) = 1.00 × 10–6 M), NIT (c(BPB) = 9.02 × 10–5 M, c(NIT) = 4.55 × 10–5 M)

Full size image

The isomolar series and molar ratios approach were used to calculate the stoichiometric coefficients of the reaction between studied CCBs and BPB. The isomolar series technique (Job's method) is one of the most well-liked and often applied approaches for determining the ratio of components. The primary idea behind Job's approach is to combine the components under study in various ratios while maintaining a constant volume ratio. The drug-dye complex's stoichiometry was determined to be 1:1 (Fig. 10).

Fig. 10
figure 10

Study of stoichiometric coefficients by the reaction of selected CCBs with BPB at λmax = 596 nm, using Job’s method of continuous variations (AML (c(BPB) = 6.00 × 10–4 M, c(AML) = 6.00 × 10–4 M), LAC (c(BPB) = 5.00 × 10–4 M, c(LAC) = 5.00 × 10–4 M, C% MeOH = 8%), LAML (c(BPB) = 1.00 × 10–4 M, c(LAML) = 1.00 × 10–4 M), NIF (c(BPB) = 6.00 × 10–4 M, c(NIF) = 6.00 × 10–4 M), NIM (c(BPB) = 5.00 × 10–4 M, c(NIM) = 5.00 × 10–4 M), NIT (c(BPB) = 9.02 × 10–4 M, c(NIT) = 9.10 × 10–4 M)

Full size image

The ratio of reacting components as 1 to 1 was also confirmed by the method of molar ratios. Molar ratios are a useful tool for analyzing the relationship between the concentration of one solution component's absorption and the constant concentration of another (first curve) and the amount of the second component's absorption that the first component's constant concentration (second curve) depends on. A saturation curve intersecting at the coefficient of the variable-concentration component is equivalent to that, as shown in Fig. 11.

Fig. 11
figure 11

Study of stoichiometric coefficients by the reaction of selected CCBs with BP B at λmax = 596 nm, using molar ratio method: (a)—AML (c(BPB) = 6.00 × 10–4 M, c(AML) = 6.00 × 10–4 M); (b)—LAC (c(BPB) = 5.00 × 10–4 M, c(LAC) = 5.00 × 10–4 M, C% MeOH = 8%); (c)—LAML (c(BPB) = 1.00 × 10–4 M, c(LAML) = 1.00 × 10–4 M); (d)—NIF (c(BPB) = 6.00 × 10–4 M, c(NIF) = 6.00 × 10–4 M); (e)—NIM (c(BPB) = 5.00 × 10–4 M, c(NIM) = 5.00 × 10–4 M); (f)—NIT (c(BPB) = 9.02 × 10–4 M, c(NIT) = 9.10 × 10–4 M)

Full size image

The optimal parameters for CCBs spectrophotometric analysis via complex formation using BPB were as follows: detection wavelength—596 nm, reaction time—5 min, ratio of reacting components—1:1, operating temperature—25 ± 2 °C. The optimal solvent and BPB concentration are presented in Table S1 (Appendix G).

Validation of the spectrophotometric methods for the determination of dihydropyridines CCBs

The proposed spectrophotometric methods for determination of studied CCBs in tablets have been validated for the following parameters: robustness, accuracy and precision, linearity, and range of application, in accordance with the requirements of the guidelines of the International Conference on Harmonization (ICH) [61]. Robustness (reaction time, reagent volume change, and absorbance stability) was assessed during the method's development. Previous development studies have shown that changes performed throughout the robustness research within ± 10% do not significantly change the absorbance value (Table 4). All calculated results fall between 98.0% and 102.0% and met the acceptance criteria. Regression analysis was used to assess the linearity of the proposed spectrophotometric methods for the determination of CCBs by reaction with BPB at λmax 596 nm. Linearity results for the assessed spectrophotometric procedures are shown in Table 5. It was shown that determination of AML had the broadest range. The correlation coefficients were higher than 0.998 for all analytes, indicating that all of the analytical procedures linearity was acceptable. Three drug concentration levels were examined in order to evaluate the accuracy of the proposed methods. The obtained results showed a significant agreement between the measured and real ones, as shown in Table 6, proving the correctness of the established procedures. The average recovery percentage varies between 99.0% and 101.0%. A recovery value between 98.0% and 102.0% was assigned to each concentration level. For each recovery value, the RSD was less than 1.28%. The degree to which the experimental outcomes agreed with one another was assessed using intra- and inter-day precision evaluation. Inter-day precision was attained by tracking the same concentrations for three days in a row, whereas intra-day precision was attained by repeating the measurement of three analyte concentration levels at three different times of the day. The obtained results are displayed in Table 7.

Table 4 Robustness of the proposed methods
Full size table
Table 5 Linearity results for the evaluated spectrophotometric procedures
Full size table
Table 6 Accuracy assessment of the proposed spectrophotometric determinations of CCBs using BPB
Full size table
Table 7 Intra- and inter-day precision assessment
Full size table

Application to tablet analysis

The suggested methods were effectively employed to determine the studied CCBs in their tablet dosage forms. Table 8 demonstrates favorable outcomes indicating high accuracy. The developed methods are colorimetric and therefore does not require a UV instrument to quantify these drugs. The proposed methods can be used to control the quality of dosage forms, study the stability and impact of changes on dosage forms while implementation of new manufacturers of excipients, when changing manufacturing technology, changing the composition of drugs and other processes of the life cycle of dosage forms of studied CCBs. However, the proposed methods have limitations. It is not possible to use developed methods for CCBs determination in the presence of other APIs which may affect the analytical reaction.

Table 8 The results of the quantitative determinations of CCBs in tablets
Full size table

Greenness assessment

While the developing analytical methods for the quantification, an important aspect is the implementation of the principles of «green» chemistry, which minimize the negative impact of chemicals on the environment and human health [62,63,64,65,66]. «Green» chemistry is a philosophy of modern chemical research, which is aimed at the use of renewable raw materials, the elimination of extraction, the use of small quantities of reagents and a tested sample, the use of catalysts to increase efficiency, reduce waste.

Scientists use a variety of tools and approaches to calculate the «greenness», one of which is the Analytical GREEnness (AGREE) method – this is an analytical calculator that greatly facilitates the calculation of the environmental friendliness and safety of the developed methodology, which shows the result of the analysis in the form of a certain pictogram, which takes into account the impact of each analytical operation on the result obtained, which is marked by a variation in color from ecological-green to dangerous-red [64].

Nowadays, the most modern valuable matrices such as modified green analytical procedure index (MOGAPI) [65] and Complementary Green Analytical Procedure Index (Complex MOGAPI) [66] are used to evaluate the greenness of analytical methods.

Table 2 presents the obtained «green» pictograms of the spectrophotometric methods of the studied analytes for reactions with dyes described in the scientific literature using the AGREE and MOGAPI tools. We understood the problems in the environmental safety of the analytical methods at the stage of planning our research, as we calculated the «greenness» score by the AGREE tool. The highest «greenness» score (0.76) was given to the method of the spectrophotometric determination of AML by reaction with crystal violet, which involved the use of acidic medium, potassium bromide and potassium bromate (Al-Mohsen Khdadad [57]). Such an excellent result can be explained by the time of the methodology (2022 year) and the use of modern approaches. The lowest «greenness» score (0.67) was obtained in the methods [52, 55, 56], which was due to the use of the toxic solvent chloroform. MOGAPI tool identified major problems such as extraction and use of toxic solvents. Figures 12, 13 show the obtained AGREE and MOGAPI scores the proposed methods. As can be seen from the pictograms on Fig. 12, the AGREE assessment scores for the methods for the determination of AML, NIT, NIF, LAML was 0.74 and 0.68 for NIM, LAC. It was worth noting that operations 7 and 10 were marked in yellow in all the methods, which indicates significant waste and the type of solvent. Parameter 11 (toxicity of the reagent) was marked in orange for NIM and LAC, due to the use of acetonitrile solvent. As can be seen from Fig. 13, the MOGAPI assessment scores for methods for the determination of AML, NIT, NIF, LAML was 0.72 and 0.70 for NIM, LAC, which was consistent with the results of the AGREE tool and indicates acceptable green analysis.

Fig. 12
figure 12

AGREE assessment scores for the proposed methods used for the determination of AML (a), NIT (b), NIF (c), LAML (d), NIM (e), LAC (f)

Full size image
Fig. 13
figure 13

MOGAPI assessment scores for the proposed methods used for the determination of AML (a), NIT (b), NIF (c), LAML (d), NIM (e), LAC (f)

Full size image

Conclusion

In this work, thorough scientific research was carried out with the presentation of the method of selection of the optimal reagent, solvent, analytical wavelength and spectrophotometric methods for determining six CCBs were developed. In addition, the six studied CCBs were quantified using new «green», easy-to-implement, and cost-effective spectrophotometric approaches. The resulting ionic associates did not need to be extracted with organic solvents, which made the techniques safer for the environment. In addition, the proposed approach was more efficient in terms of time reliability, sensitivity and «greenness» than other recorded spectrophotometric methods. Moreover, the described approach can be easily implemented for routine pharmaceutical analysis.

Availability of data and materials

Data is provided within the manuscript or supplementary information files.

References

  1. Hypertension – World Health Organization. https://www.who.int/health-topics/hypertension#tab Accessed on 31 May 2024

  2. A Global Brief on Hypertension - World Health Organization. http://apps.who.int/iris/bitstream/10665/79059/1/WHO_DCO_WHD_2013.2_eng.pdf. Accessed on 31 May 2024.

  3. Kario K, Hoshide S, Mogi M. Digital hypertension 2023: concept, hypothesis, and new technology. Hypertens Res. 2022;45(10):1529–30.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Flack JM, Adekola B. Blood pressure and the new ACC/AHA hypertension guidelines. Trends Cardiovasc Med. 2020;30(3):160–4.

    Article  PubMed  Google Scholar 

  5. Xu SK, Huang QF, Zeng WF, Sheng CS, Li Y, Wang JG. A randomized multicenter study on ambulatory blood pressure and arterial stiffness in patients treated with valsartan/amlodipine or nifedipine GITS. J Clin Hypertens (Greenwich). 2019;21(2):252–61.

    Article  CAS  PubMed  Google Scholar 

  6. Nitrendipine. PubChem – National Library of Medicine. https://pubchem.ncbi.nlm.nih.gov/compound/Nitrendipine Accessed on 31 May 2024

  7. Yusupova KHF, Abdullaeva GJ, Khamidullaeva GA, Ibrohimov NN. Neuroprotective efficacy of combined antihypertensive treatment with the inclusion of nitrendipine in patients with arterial hypertension. Eur Heart J. 2023;44(2):655.

    Google Scholar 

  8. DailyMed – National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/browse-drug-classes.cfm Accessed on 31 May 2024

  9. Kecskés S, Menyhárt Á, Bari F, Farkas E. Nimodipine augments cerebrovascular reactivity in aging but runs the risk of local perfusion reduction in acute cerebral ischemia. Front Aging Neurosci. 2023;15:1175281.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Chatki P, Tabassum S. Analytical methods of dihydropyridines based calcium channel blockers - amlodipine, lacidipine, isradipine, nifedipine, felodipine, cilnidipine and its related formulations: a review. Asian J Res Chem. 2021;14:221–34.

    Article  Google Scholar 

  11. Fares H, Di Nicolantonio JJ, O’Keefe JH, Lavie CJ. Amlodipine in hypertension: a first-line agent with efficacy for improving blood pressure and patient outcomes. Open Heart. 2016;3(2): e000473.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Abdulsahib WK. The effect of levamlodipine in glucose-induced acute model of glaucoma in rabbits. J Med Sci. 2021;9:505–9.

    Google Scholar 

  13. Li X, Wang C, Li T, et al. Bioequivalence of levamlodipine besylate tablets in healthy Chinese subjects: a single-dose and two-period crossover randomized study. BMC Pharmacol Toxicol. 2020;21:80.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Dessai AA, Kantak MN, Dcruz CEM, Kumar L, Bhide PJ, Shirodkar RK. Formulation and characterization of nanoparticulate drug carrier system for lacidipine. Assay Drug Dev Technol. 2023;21(7):309–24.

    Article  CAS  PubMed  Google Scholar 

  15. Nachiket S, Bhosale DM, Pallavi B. Gaikwad an overview on estimation of lacidipine from bulk and formulation. Asian J Pharm Anal. 2021;11(3):223–6.

    Google Scholar 

  16. Kumari K, Sinha R, Toppo MS, Mishra P, Alam S, Majhee L. Blood pressure reducing potential and renoprotective action of cilnidipine among hypertensive patients suffering from chronic kidney disease: a meta-analysis. Cureus. 2023;15(4): e37774.

    PubMed  PubMed Central  Google Scholar 

  17. USP Monographs: Nimodipine. https://pharmacopeia.cn) Accessed on 31 May 2024

  18. General notices and requirements -USP. https://www.uspnf.com/sites/default/files/usp_pdf/EN/USPNF/amlodipineBesylateTabletsm3575.pdf Accessed on 31 May 2024

  19. Caglayan MG, Palabiyik IM, Bor M, Onur F. Optimisation and validation of liquid chromatographic and partial least-squares methods for simultaneous determination of enalapril maleate and nitrendipine in pharmaceutical preparations. Chem Pap. 2011;65:754–60.

    Article  CAS  Google Scholar 

  20. Channabasavaraj KP, Nagaraju PT, Shantha KP, Reddy S. Reverse phase HPLC method for determination of lacidipine in pharmaceutical preparations. Int J Pharm Sci Rev Res. 2010;5(2):111–4.

    CAS  Google Scholar 

  21. Lingfang D, Kun L, Shan G, Wenyi W, Yinghua F, Jingying Z, Jie Y, Weifeng D. Sensitive and effective method with 96-well plate for determination of levamlodipine in human plasma using LC–MS/MS. Anal Biochem. 2024;691: 115556.

    Article  Google Scholar 

  22. Hao C, Lan L, Shuai S, Yan D, Xiaoqin J, PeiPei D, Chenlin S, Xiaohui H. Determination of lacidipine in human plasma by LC-MS/MS: Application in a bioequivalence study. Int J Clin Pharmacol Ther. 2018;56(10):493–500.

    Article  Google Scholar 

  23. Qi Y, Zhang X. Determination of enantiomeric impurity of levamlodipine besylate bulk drug by capillary electrophoresis using carboxymeth yl-β-cyclodextrin. Cell Biochem Biophys. 2014;70(3):1633–7.

    Article  CAS  PubMed  Google Scholar 

  24. Linlin X, Zhaoqing L, Tancong L, Xun T. Probing the interaction between levamlodipine and hemoglobin based on spectroscopic and molecular docking methods. Spectrochim Acta A Mol Biomol Spectrosc. 2019;5(223): 117306.

    Google Scholar 

  25. Zhaoqing L, Xiaojian H, Zheng J, Tuo X. Investigation of the binding properties between levamlodipine and HSA based on MCR-ALS and computer modeling. Spectrochim Acta A Mol Biomol Spectrosc. 2021;245:118929.

    Article  Google Scholar 

  26. Refaat EM, Wahid NN, Sayed AS, Aziz MA. Determination of Aliskiren Hemifumarate and amlodipine Besylate in their combined dosage form by different spectrophotometric methods. Curr Pharm Anal. 2016;12(4):391–8.

    Article  Google Scholar 

  27. Sharkawi MM, Mohamed NR, El-Saadi MT, Amin NH. Five spectrophotometric methods for simultaneous determination of Amlodipine besylate and celecoxib in presence of its toxic impurity. Spectrochim Acta A Mol Biomol Spectrosc. 2021;263: 120137.

    Article  CAS  PubMed  Google Scholar 

  28. Attimarad M, Venugopala KN, Aldhubiab BE, Nair AB, SreeHarsha N, Pottathil S, Akrawi SH. Development of UV spectrophotometric procedures for determination of amlodipine and celecoxib in formulation: use of scaling factor to improve the sensitivity. J Spectrosc. 2019;1:10.

    Google Scholar 

  29. Abed SS. Cloud-point extraction and spectrophotometric determination of Nifedipine in pharmaceutical dosage forms. Sys Rev Pharm. 2020;11:7.

    Google Scholar 

  30. Bhosle D, Deshmane P, Kamble A. UV spectrophotometric method development and validation of nifedipine in bulk and formulation. Int J Res Anal Rev. 2021;8(3):260–5.

    Google Scholar 

  31. Mohammad MA, Mahrouse MA, Amer EAH, Elharati NS. Simultaneous determination of enalapril maleate and nitrendipine in tablets using spectrophotometric methods manipulating ratio spectra. Spectrochim Acta A Mol Biomol Spectrosc. 2021;244:1188941.

    Article  Google Scholar 

  32. Belal F, Sharaf El Din M, Tolba M, Alaa H. Micelle-enhanced spectrofluorimetric method for determination of lacidipine in tablet form Application to content uniformity testing. Luminescence. 2014. https://doiorg.publicaciones.saludcastillayleon.es/10.1002/bio.2823.

    Article  PubMed  Google Scholar 

  33. Rahman N, Azmi S. Spectrophotometric determination of amlodipine besylate by charge-transfer complex formation with p-chloranilic acid. Anal Sci. 2000;16:1353–6.

    Article  CAS  Google Scholar 

  34. Rahman N, Najmul S, Azmi H. Spectrophotometric method for the determination of amlodipine besylate with ninhydrin in drug formulations. Il Farmaco. 2001;56(10):731–5.

    Article  CAS  PubMed  Google Scholar 

  35. Ravichandran V, Ravichandran VS, Raghuraman V, Sankar V. Spectrophotometric method for the determination of lacidipine in tablets. Indian J Pharm Sci. 2004;66(6):797–9.

    CAS  Google Scholar 

  36. Rahman N, Singh M, Hoda MN. Application of oxidants to the spectrophotometric determination of amlodipine besylate in pharmaceutical formulations. Farmaco. 2004;59(11):913–9.

    Article  CAS  PubMed  Google Scholar 

  37. Askal HA, Osama A, Sayed A, Mohamed EH. Spectrophotometric and spectrofluorimetric determination of 1,4-dihydropyridine drugs using potassium permanganate and cerium (IV) ammonium sulphate. Bull Pharm Sci. 2010;33:201–15.

    CAS  Google Scholar 

  38. Revanasiddappa H. Spectrophotometric methods for the determination of nimodipine in pure and in pharmaceutical preparations. Jordan J Chem. 2011;6(4):413–22.

    CAS  Google Scholar 

  39. Revanasiddappa HD, Deepakumari HN, Mallegowda SM, Vinay KB. Facile spectrophotometric determination of nimodipine and nitrazepam in pharmaceutical preparations. Analele UniversităŃii din Bucureşti Chimie. 2011;20(2):189–96.

    CAS  Google Scholar 

  40. Moorthi C, Aju M, Elsadig P, Sumithira G. Spectrophotometric determination of lacidipine in bulk and tablet dosage form. J Appl Pharm Sci. 2011;01(05):209–13.

    Google Scholar 

  41. Hemavathi ND, Hosakere DR. A sensitive spectrophotometric estimation of nimodipine in tablets and injection using phloroglucinol. Spectroscopy. 2013;5:1–7.

    Google Scholar 

  42. Hamd M, Derayea S, Abdelmageed O, Askal H. Spectrophotometric method for determination of five 1,4-dihydropyridine drugs using n-bromosuccinimide and indigo carmine dye. Int J Spectrosc. 2013;1:7.

    Google Scholar 

  43. Hamd M, Derayea S, Abdelmageed O, Askal H. A novel spectrophotometric method for determination of five 1,4-dihydropyridine drugs in their tablets and capsules using vanillin reagent. Am J Analyt Chem. 2013;4:148–57.

    Article  Google Scholar 

  44. Marzouq MA, Aboelhamd M, Ahmed SA, Askal HF, Saleh GA. Spectrophotometric determination of some 1,4-dihydropyridine drugs in their pharmaceutical preparations and spiked human plasma. Der Pharma Chem. 2015;7(8):105–11.

    CAS  Google Scholar 

  45. Tulasamma P, Venkateswarlu P. Spectrophotometric determination of nifedipine in pharmaceutical formulations, serum and urine samples via oxidative coupling reaction. Arab J Chem. 2016;9(2):1603–9.

    Article  Google Scholar 

  46. Sulyma M, Vasyuk S, Zhuk Y, Kaminskyy D, Chupashko O, Ogurtsov V. New spectrophotometric method of amlodipine besylate determination and its validation. Chem Chem Technol. 2018;12(4):429–33.

    Article  CAS  Google Scholar 

  47. Khachornsakkul K, Dungchai W. A portable reflective absorbance spectrophotometric smartphone device for the rapid and highly accurate determination of amlodipine in pharmaceutical formulation and human urine samples. Anal Sci. 2021;37:963–9.

    Article  CAS  PubMed  Google Scholar 

  48. Hanan HA, Salim AM. The use of charge transfer reaction for the spectrophotometric estimation of nimodipine in the bulk, pharmaceutical formulation and biological fluids. Riv Ital Filos Anal Jr. 2023;14(2):264–77.

    Google Scholar 

  49. Hanan HA, Salim AM. A spectrophotometric approach for estimating nimodipine by oxidative-coupling reaction with 4-aminoantipyrine in its tablet and biological fluids. Med Clin Res. 2023;8(9):01–10.

    Google Scholar 

  50. Hanan HA, Salim AM. Improved spectrophotometric estimation of nimodipine in the pharmaceutical formulation and biological fluids. Pak J Anal Environ Chem. 2023;24(2):185–96.

    Article  Google Scholar 

  51. Magnaghi LR, Zanoni C, Alberti G, Biesuz R. The colorful world of sulfonephthaleins: current applications in analytical chemistry for “old but gold” molecules. Anal Chim Acta. 2023;1281: 341807.

    Article  CAS  PubMed  Google Scholar 

  52. Sridhar K, Sastry CSP, Reddy MN, Sankar DG, Srinivas KR. Spectrophotometric determination of amlodipine besylate in pure forms and tablets. Anal Lett. 1997;30(1):121–33.

    Article  CAS  Google Scholar 

  53. Singhvi SI, Chaturvedi C. Visible spectrophotometric methods for estimation of amlodipine besylate form tablets. Indian J Pharm Sci. 1998;309:310.

    Google Scholar 

  54. Rahman N, Khan NA, Azmi SNH. Extractive spectrophotometric methods for the determination of nifedipine in pharmaceutical formulations using bromocresol green, bromophenol blue, bromothymol blue and eriochrome black T. Il Farmaco. 2004;59(1):47–54.

    Article  CAS  PubMed  Google Scholar 

  55. Asgar A, Khaja P, Raju SA, Aejaz A. Visible spectrophotometric determination of amlodipine in pharmaceutical formulation and bulk drug by using bromophenol blue. Int J Pharm Pharm Sci. 2010;2(2):128–9.

    Google Scholar 

  56. Raghad A, Aya A, Amir AS. Spectrophotometric determination of amlodipine besylate in pure form and pharmaceutical formulation using amido black. Res J Pharm and Tech. 2019;12(7):3389–92.

    Article  Google Scholar 

  57. Al-Mohsen Khdadad ZA, Khaleel AI, Rashid QN. Spectrophotometric methods for estimation of amlodipine besylate in pure form and in it’s pharmaceutical formulations. Int J Health Sci. 2022;6(S1):7726–41.

    Article  Google Scholar 

  58. Nguyen TD, Le TH, Nguyen TH, Hoang TTM. Extractive spectrophotometric determination of nimodipine through ion-pair complex formation with bromothymol blue. J Sci and Technol. 2022;17(01):5–16.

    Google Scholar 

  59. Al-Shwaiyat MKEA, Galkina K, Sidorova L, Zhuk L, Matorina K, Chernyavskaya A, Khudyakova S, Vishnikin S. Use in pharmaceutical analysis of ionic association complexes formed between sulphonephthalein dyes and nitrogen -containing compounds in medium of organic solvents. J Chem Technol. 2023;31(4):713–26.

    CAS  Google Scholar 

  60. Bromophenol Blue. PubChem – National Library of Medicine. https://pubchem.ncbi.nlm.nih.gov/compound/Bromophenol-Blue Accessed on 31 May 2024

  61. ICH Validation of Analytical Procedures: Text and Methodology, Q2 (R2), Geneva. 2023. ICH_Q2(R2)_Guideline_2023_1130.pdf (Accessed on 24 June 2024).

  62. Gałuszka A, Konieczka P, Migaszewski Z, Namiesnik J. Analytical eco-scale for assessing the greenness of analytical procedures. Trends Anal Chem. 2012;37:61–72.

    Article  Google Scholar 

  63. Płotka-Wasylka J. A new tool for the evaluation of the analytical procedure: green analytical procedure index. Talanta. 2018;181:204–9.

    Article  PubMed  Google Scholar 

  64. Pena-Pereira F, Wojnowski W, Tobiszewski M. AGREE-analytical greenness metric approach and software. Anal Chem. 2020;92:10076–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Mansour F, Płotka-Wasylka J, Locatelli M. Modified GAPI (MoGAPI) tool and software for the assessment of method greenness: case studies and applications. Analytica. 2024;5:451–7.

    Article  Google Scholar 

  66. Mansour F, Omer K, Płotka-Wasylka J. A total scoring system and software for complex modified GAPI (ComplexMoGAPI) application in the assessment of method greenness. Green Analytical Chemistry. 2024;10: 100126.

    Article  Google Scholar 

Download references

Funding

The research leading to these results has received funding from the Ministry of Health of Ukraine, under the project number 0124U000065.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine

    Mariana Horyn, Liubomyr Kryskiw, Tetyana Kucher, Nadiya Zarivna, Olha Poliak & Liliya Logoyda

Authors
  1. Mariana Horyn
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Liubomyr Kryskiw
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Tetyana Kucher
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Nadiya Zarivna
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Olha Poliak
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Liliya Logoyda
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

Horyn Mariana, Liubomyr Kryskiw, Tetyana Kucher, Nadiya Zarivna, Liliya Logoyda: Methodology and writing the original draft, Validation and reviewing, Horyn Mariana, Liubomyr Kryskiw, Tetyana Kucher, Nadiya Zarivna, Olha Poliak, Liliya Logoyda: Validation and reviewing, Liliya Logoyda: reviewing and publishing editing and supervision.

Corresponding author

Correspondence to Liliya Logoyda.

Ethics declarations

Ethical approval and consent to participate

Not applicable.

Ethical Guidelines

Guidelines according to BMC journal.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Horyn, M., Kryskiw, L., Kucher, T. et al. Novel ecofriendly spectrophotometric methods for the determination of six dihydropyridines calcium channel blockers through derivatization with sulfophtalein dye: application to tablet analysis. BMC Chemistry 19, 8 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s13065-024-01378-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s13065-024-01378-x

Keywords

BMC Chemistry

ISSN: 2661-801X

Contact us