DEVELOPMENT OF THE HPLC METHOD FOR THE DETERMINATION OF CAPTOPRIL IN TABLETS USING SALTS OF CHAOTROPIC ANIONS
DOI:
https://doi.org/10.11603/1811-2471.2025.v.i4.15776Keywords:
captopril, quantitative determination, HPLC, chaotropes, greennessAbstract
SUMMARY. Analysis of captopril using reversed-phase liquid chromatography is not a complicated task; however, due to the proline structure, captopril may elute near the dead volume, which creates challenges in performing quantitative determination. The second problem is the tendency of the captopril peak to deform with tailing and to produce an asymmetrical peak. In our work, we propose the use of chaotropic anion salts in the mobile phase on a C18 column as a promising approach to effective analytical development, which will allow improving the retention and peak shape of captopril.
The aim – to develop a rapid, simple, and green HPLC method for determining captopril in tablets using salts of chaotropic anions.
Material and Methods. In our work, we used a Shimadzu LC-2050 C Agilent 1260 liquid chromatograph with a diode-array detector (Japan), LabSolutions software, and a Zorbax SB-C18 chromatographic column (150 × 4.6 mm, 3.5 μm). Captopril standard substance (purity ≥99 %, HPLC) was purchased from Sigma-Aldrich Chemicals Co., and Captopril tablets (25 mg) were from PJSC Kyivmedpreparat, ARTERIUM.
Results. Under the conditions of the mobile phase ACN–water, PF6− exhibits the highest retention and is the most lipophilic ion in the Hofmeister series. PF6− has the highest degree of charge delocalization and the highest polarizability, which facilitates its dispersion (or van der Waals) interactions. As a result of numerous experimental studies, the optimal chromatographic conditions for determining captopril in tablets have been established: chromatographic column Zorbax SB-C18 (150 x 4.6 mm, 3.5 µm), mobile phase – 30 % ACN and 70 % buffer solution pH 2.10 (0.25 % KPF6, 0.1 % HCLO4, 0.1 % KH2PO4), column temperature – 40 °C, detection at a wavelength of 200 nm, flow rate – 1.0 ml/min, solvent – mobile phase. The linearity of the analytical method was studied in the range of 40–120 µg/mL using the least squares method, and the regression equation (y=12096x-45214) was calculated with a correlation coefficient (R²=0.9998). The limit of detection (LOD) was 8.51 µg/mL, and the limit of quantification (LOQ) was 25.80 µg/mL. Using the most advanced tools for studying greenery–AGREE (score 0.72), MoGAPI (score 81), Complex MoGAPI (score 81), AGSA (score 73.61), CaFRI (score 74), and CACI (score 82)—it has been determined that the proposed HPLC method is ecologically safe.
Conclusions. A rapid, simple, and green HPLC method for the determination of captopril in tablets using salts of chaotropic anions has been developed. The proposed HPLC method allows for the quantitative determination of captopril in tablets, obtaining a symmetrical peak that does not elute near the dead volume. In addition, the developed HPLC method can be used for the analysis of related impurities.
References
PubChem – National Library of Medicine. Available at: https://pubchem. ncbi.nlm.nih.gov/compound/Accessed on 31 May 2025
Derzhavna farmakopeya Ukrayiny: v 3 t. 2-e vyd. [State Pharmacopoeia of Ukraine: in 3 volumes, 2nd edition]. Kharkiv: State Enterprise "Ukrainian Scientific and Expert Pharmacopoeial Center for the Quality of Medicinal Products", 2014; 2: 724. Ukrainian
Derzhavna farmakopeya Ukrayiny: v 3 t. 2-e vyd. [State Pharmacopoeia of Ukraine: in 3 volumes, 2nd edition]. Kharkiv: State Enterprise "Ukrainian Scientific and Expert Pharmacopoeial Center for the Quality of Medicinal Products", 2014; 3: 724. Ukrainian
Jebaslinhepzybai B, Velmurugan C, Chenthilnathan A. Validation of the RP-HPLC method for analysis of captopril in pharmaceutical tablets. Der Pharmacia Sinica. 2016;7(4):1–6.
Leanpolchareanchai J, Suksiriworapong J. Validation of analytical method for captopril extemporaneous preparations by high performance liquid chromatography. MU J. Pharm. Sci. 2015;42(2):85–92. DOI: 10.14456/mujps. 2015.11
Sultan N, Naveed S, Arayne MS. RP-HPLC Method for the simultaneous determination of captopril and H2-receptor antagonist: Application to interaction studies. Med. Chem. 2013;3:183–187. DOI: 10.4172/2161-0444. 1000136 DOI: https://doi.org/10.4172/2161-0444.1000136
Huang T et al. Simultaneous determination of captopril and hydrochlorothiazide in human plasma by reverse-phase HPLC from linear gradient elution. Journal of Pharmaceutical and Biomedical Analysis 2006;41(2):644–648. DOI: 10.1016/j.jpba.2005.12.007 DOI: https://doi.org/10.1016/j.jpba.2005.12.007
Papanov S, Hadjieva B, Koleva N. Rapid RP-HPLC method for estimation of captopril from tablet dosage form. IJBPAS. 2014;3(3):317–325.
Sultana N, Arayne MS, Naveed S. Simultaneous quantitation of captopril and NSAID’s in API, dosage formulations and human serum by RP-HPLC. J. Chin. Chem. Soc. 2010;57(1):62–67. DOI: https://doi.org/10.1002/jccs.201000010
Logoyda L, Korobko D, Samohalska O, Berdey I, Kuchmerovska T. Development of methodology for identification of captopril in medicines. Asian Journal of Pharmaceuticals. 2016;10(3):168–171. DOI: https://doi.org/10.22159/ajpcr.2017.v10i3.15841
Kazakevich YV, Lobrutto R. HPLC for pharmaceutical scientists. John Wiley & Sons. 2006. DOI: https://doi.org/10.1002/0470087951
ICH Validation of Analytical Procedures: Text and Methodology, Q2 (R2), Geneva. 2023. Available from https://database.ich.org/sites/default/files/ICH_Q2%28R2%29_Guideline_2023_1130.pdf
Pena-Pereira F, Wojnowski W, Tobiszewski M. AGREE—Analytical GREEnness metric approach and software. Analytical chemistry. 2020;92(14):10076-10082. DOI: 10.1021/acs.analchem.0c01887 DOI: https://doi.org/10.1021/acs.analchem.0c01887
Mansour FR, Płotka-Wasylka J, Locatelli M. Modified GAPI (MoGAPI) tool and software for the assessment of method greenness: case studies and applications. Analytica. 2024;5(3):451-457. DOI: 10.3390/analytica5030030 DOI: https://doi.org/10.3390/analytica5030030
Mansour FR, Omer KM, 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. DOI: 10.1016/j.greeac.2024.100126 DOI: https://doi.org/10.1016/j.greeac.2024.100126
Mansour FR, Bedair A, Belal F, Magdy G, Locatelli M. Analytical Green Star Area (AGSA) as a new tool to assess greenness of analytical methods. Sustainable Chemistry and Pharmacy. 2025;46:102051. DOI: 10.1016/j.scp.2025.102051 DOI: https://doi.org/10.1016/j.scp.2025.102051
Mansour FR, Nowak, P. M. Introducing the carbon footprint reduction index (CaFRI) as a software-supported tool for greener laboratories in chemical analysis. BMC chemistry. 2025;19(1):121. DOI: 10.1186/s13065-025-01486-2 DOI: https://doi.org/10.1186/s13065-025-01486-2
Mansour FR, Bedair A, Locatelli, M. Click analytical chemistry index as a novel concept and framework, supported with open source software to assess analytical methods. Advances in Sample Preparation. 2025;14:100164. DOI: 10.1016/j.sampre.2025.100164 DOI: https://doi.org/10.1016/j.sampre.2025.100164
