DEVELOPMENT OF THE HPLC METHOD FOR THE DETERMINATION OF NIFEDIPINE IN DRUGS USING THE APPROACH “QUALITY BY DESIGN”

Abstract

Introduction. Calcium channel blockers (CCBs) are among the basic drugs used in the treatment of hypertension (HT). To ensure the quality control of drugs at any stage of the life cycle, reliable, fast, sensitive and safe methods for the quantitative determination of their active pharmaceutical ingredients are required. Nifedipine is a 1,4-dihydropyridine derivative by chemical structure. Existing methods for the determination of nifedipine lack experimental planning, which in turn leads to excessive use of solvents and an increase in the time required to develop the method due to a series of negative experiments. The aim of the work was to develop an accessible, simple and safe HPLC method for the determination of nifedipine in drugs using Quality by Design (QbD) approaches. Research Methods. In this study used a Shimadzu LC-2050 C liquid chromatograph with a diode array detection (DMD) and LabSolutions software. Different types of columns were used as stationary phases when studying the versatility and accessibility of the developed method: Luna C8, Luna C18, Zorbax C8 Stable Bond (SB), InertClone ODS and Zorbax SB Phenyl. Nifedipine СRS (purity ≥ 98 %) manufactured by Sigma-Aldrich Chemicals Co. (St. Louis, MO, USA), Nifedipine tablets 20 mg manufactured by LekKhim PrJSC. Results and Discussion. To plan the experiment on the development of HPLC method for the determination of nifedipine in drugs was used a modern QbD approach. The basic elution conditions were based on isocratic elution of nifedipine with a mobile phase consisting of: acetonitrile-methanol – 0.7 % triethylamine with pH 3.05 in the ratios 30–35–35. Chromatographic conditions: temperature – 30 °C, mobile phase flow rate – 1 ml/min, detection at wavelength – 237 nm, total detection time up to 4 min. The proposed method was tested on different columns: Luna C8 (150 × 4.6 mm, 3 μm), Luna C18 (100 × 4.6 mm, 3 μm), InertClone ODS (150 × 4.6 mm, 3.5 μm), Zorbax SB C8 (150 × 4.6 mm, 3.5 μm). According to the results, it can be concluded that the proposed approach for the determination of nifedipine is universal and expands the horizon of the use of the developed method for laboratories with a limited number of chromatographic columns. Validation of the HPLC method was carried out in accordance with the requirements of the ICH for the following parameters: linearity, accuracy, precision and robustness. The LOD and LOQ of the method were 2.33 μg/ml and 7.08 μg/ml, respectively. The range of application was from 10 to 50 μg/ml. According to the calculations performed using the MOGAPI, CaFRI, AGSA and CACI tools, the overall environmental score of the developed method was 79, 69.44, 77 and 78, respectively. The obtained values confirm that the proposed HPLC method was developed in accordance with the basic postulates of “green” chemistry using modern chromatographic approaches. Conclusions. An accessible, rapid and safe HPLC method for the determination of nifedipine in tablets using QbD principles has been developed. The HPLC method for the quantitative determination of nifedipine can be used in laboratories with a limited budget, as it satisfies the suitability parameters of the chromatographic system on various types of columns.