Method Development and Validation for the Determination of Potential Impurities Present in Olmesartan Medoxomil and Hydrochlorothiazide in Fixed Dose Combination Drug Product by Using Reverse Phase – Ultra-Performance Liquid Chromatography Coupled with Diode-Array Detector

Abstract

A simple, sensitive, and reproducible ultra-performance liquid chromatography (UPLC) method for the determination of nine known potential impurities present in Olmesartan medoxomil and Hydrochlorothiazide tablets in fixed dose combination drug product was developed. Chromatographic separation was achieved between impurities at satisfactory level using Acquity UPLC HSS T3, 100 mm length  2.1 mm id with 1.8 µm particle size column. Gradient elution mode was kept using mobile phase A as 0.1% orthophosphoric acid buffer adjusted the pH 2.5 and acetonitrile as mobile phase B. Flow rate was kept at 0.5 mL min À1 with a monitoring wavelength of 225 nm. The method is fast and uses less consumption of solvents with shorter run time of 9 min. This can enable the separation of all known potential impurities of two active compounds in a rapid, precise, sensitive, cost, and time effective manner. The performance of the method was validated according to the present ICH guidelines for specificity, limit of detection, limit of quantification, linearity, accuracy, precision, solution stability, and robustness. The method is fast and is suitable for high-throughput analysis of the drug facilitating the processing of large-number batch samples.

Application of supercritical fluid chromatography for separation and quantitation of 15 co‐formulated binary anti‐hypertensive medications using a single elution protocol

“…The results obtained showed acceptable accuracy and precision of the assay, with no interference from the excipients present in the formulations. Further, Student's t ‐test and F ‐test were applied (at 95% confidence level) for the statistical comparison between the results obtained by applying the proposed SFC method for the binary combinations and reported methods (Bharathi, Hotha, Chatki, Satyanarayana, & Venkateswarlu, 2012; de Diego, Soto, & Mennickent, 2014; Deshmukh, Deo, Inam, & Lambat, 2018; Elgorashe, Idris, Abdelrahman, & Saeed, 2013; Gao et al, 2010; Kamble, Mahadik, Khatal, & Dhaneshwar, 2010; Karra, Pilli, Inamadugu, & Seshagiri Rao, 2012; Karvelis, Kalogria, & Panderi, 2014; Kolocouri, Dotsikas, Apostolou, Kousoulos, & Loukas, 2007; Özdemir & Akyüz, 2014; Rane, Sangshetti, & Shinde, 2008; Ravi, Inamadugu, Pilli, Sreenivasulu, & Ponneri, 2012; Shah, Parekh, et al, 2017; Srikanth, Murali, Vekaria, Rao, & Mantena, 2015; Tian, Tian, Tian, Wang, & Mo, 2008). The values found for both the test were less than the tabulated values, suggesting insignificant differences between the methods in terms of accuracy and precision (Table 5).…”

“…Özdemir and Akyüz (2014) (combination 5), Bharathi, Hotha, Chatki, Satyanarayana, and Venkateswarlu (2012) (combination 6), Kolocouri, Dotsikas, Apostolou, Kousoulos, and Loukas (2007) (for combination 7), Srikanth et al (2015) (combination 8), Rane, Sangshetti, and Shinde (2008) (for combination 9), Tian, Tian, Tian, Wang, and Mo (2008) (for combination 10), Elgorashe, Idris, Abdelrahman, and Saeed (2013) (for combination 11),…”

“…Several methods are available in literature for the separation and quantitation of these co‐formulated binary anti‐hypertensive medications. These methods include spectrophotometry (Erk, 2003; Garg, Saraf, & Saraf, 2008; Lakshmi & Lakshmi, 2010; Lakshmi & Lakshmi, 2011; Maggio, Castellano, & Kaufman, 2008; Vignaduzzo, Maggio, Castellano, & Kaufman, 2006), spectrofluorometry (Belal, Mahrous, Abdel‐Khalek, Daabees, & Khamis, 2014; Derayea, El‐din, & Mohammed, 2018; Dinç, Ertekin, & Büker, 2017; Ebeid, Elkady, El‐Zaher, El‐Bagary, & Patonay, 2014; El‐Kosasy, Tawakkol, Ayad, & Sheta, 2015; Shaalan & Belal, 2010), capillary electrophoresis (Alnajjar, 2011; Alnajjar, Idris, Attimarad, Aldughaish, & Elgorashe, 2013; Sangoi, Wrasse‐Sangoi, Oliveira, et al, 2011), infrared spectroscopy (Casian et al, 2017; Vranic & Vandamme, 2015), Raman spectroscopy (Casian et al, 2017), sequential injection chromatography (Elgorashe, Idris, Abdelrahman, & Saeed, 2013), high‐performance thin layer chromatography (Deshmukh, Deo, Inam, & Lambat, 2018; Kamble, Mahadik, Khatal, & Dhaneshwar, 2010; Pandya et al, 2017; Shah, Suhagia, Shah, & Patel, 2009), HPLC‐UV/DAD (diode array detector) (Almeida, Fernandes, Pianetti, & César, 2018; Brondi, Garcia, & Trevisan, 2017; Burnier, Vuignier, & Wuerzner, 2014; de Diego, Soto, & Mennickent, 2014; de Diego et al, 2018; Dinç, Ertekin, & Büker, 2017; Karvelis, Kalogria, & Panderi, 2014; Kurbanoglu, Gumustas, & Ozkan, 2013; Li, Lai, Xuan, Gao, & Li, 2016; Mannemala & Nagarajan, 2015; Özdemir & Akyüz, 2014; Rane, Sangshetti, & Shinde, 2008; Sangoi, Wrasse‐Sangoi, de Oliveira, et al, 2011; Tian, Tian, Tian, Wang, & Mo, 2008), ultra‐performance liquid chromatography (UPLC)‐DAD (Almeida, Fernandes, Pianetti, & César, 2018; Dinç & Ertekin, 2016; Srikanth, Murali, Vekaria, Rao, & Mantena, 2015), LC–MS/MS (Bharathi, Hotha, Chatki, Satyanarayana, & Venkateswarlu, 2012; Gao et ...…”