A Validated RP-HPLC Stability Method for the Estimation of Chlorthalidone and Its Process-Related Impurities in an API and Tablet Formulation

Low-dose thiazide and thiazide-like diuretics are widely used as first-line therapy for hypertension. Chlorthalidone, a monosulfamyl diuretic, is frequently prescribed in cases of hypertension and congestive heart failure. In this research paper, an improved reverse-phase HPLC method was developed f...

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Main Authors: Chaitali Kharat, Vaishali A. Shirsat, Yogita M. Kodgule, Mandar Kodgule
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:International Journal of Analytical Chemistry
Online Access:http://dx.doi.org/10.1155/2020/3593805
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author Chaitali Kharat
Vaishali A. Shirsat
Yogita M. Kodgule
Mandar Kodgule
author_facet Chaitali Kharat
Vaishali A. Shirsat
Yogita M. Kodgule
Mandar Kodgule
author_sort Chaitali Kharat
collection DOAJ
description Low-dose thiazide and thiazide-like diuretics are widely used as first-line therapy for hypertension. Chlorthalidone, a monosulfamyl diuretic, is frequently prescribed in cases of hypertension and congestive heart failure. In this research paper, an improved reverse-phase HPLC method was developed for the simultaneous identification and quantitation of pharmacopoeia-listed and in-house process- and degradation-related impurities of chlorthalidone in bulk drug and formulations. Chromatographic separation was carried out on a C8 column (250 × 4.6 mm; ‘5 μm particle size) at a flow rate of 1.4 mL/min with a 220 nm detection wavelength. Mobile phase A consisted of buffer solution (diammonium hydrogen orthophosphate (10 mM, pH 5.5)) and methanol at a 65 : 35 ratio (v/v), and mobile phase B consisted of buffer solution and methanol at a 50 : 50 ratio (v/v). The API and formulation were subjected to stress conditions such as acid, alkali, oxidation, thermal, and photolytic conditions. Validation studies for the in-house process impurities were performed for specificity, limit of detection (LOD), limit of quantitation (LOQ), linearity, precision, accuracy, and robustness. Thus, an improved RP-HPLC method capable of good separation of all known and unknown impurities with acceptable resolution and tailing factor was developed.
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spelling doaj-art-00cea1d103184232a64385c2c03fac0d2025-08-20T03:22:30ZengWileyInternational Journal of Analytical Chemistry1687-87601687-87792020-01-01202010.1155/2020/35938053593805A Validated RP-HPLC Stability Method for the Estimation of Chlorthalidone and Its Process-Related Impurities in an API and Tablet FormulationChaitali Kharat0Vaishali A. Shirsat1Yogita M. Kodgule2Mandar Kodgule3Bombay College of Pharmacy, Kalina, Santacruz East, Mumbai 4000098, IndiaBombay College of Pharmacy, Kalina, Santacruz East, Mumbai 4000098, IndiaIQGEN-X Pharma Pvt. Ltd., A-165, Khairane Road, Sector 2, Kopar Khairane, Navi Mumbai 400710, IndiaIQGEN-X Pharma Pvt. Ltd., A-165, Khairane Road, Sector 2, Kopar Khairane, Navi Mumbai 400710, IndiaLow-dose thiazide and thiazide-like diuretics are widely used as first-line therapy for hypertension. Chlorthalidone, a monosulfamyl diuretic, is frequently prescribed in cases of hypertension and congestive heart failure. In this research paper, an improved reverse-phase HPLC method was developed for the simultaneous identification and quantitation of pharmacopoeia-listed and in-house process- and degradation-related impurities of chlorthalidone in bulk drug and formulations. Chromatographic separation was carried out on a C8 column (250 × 4.6 mm; ‘5 μm particle size) at a flow rate of 1.4 mL/min with a 220 nm detection wavelength. Mobile phase A consisted of buffer solution (diammonium hydrogen orthophosphate (10 mM, pH 5.5)) and methanol at a 65 : 35 ratio (v/v), and mobile phase B consisted of buffer solution and methanol at a 50 : 50 ratio (v/v). The API and formulation were subjected to stress conditions such as acid, alkali, oxidation, thermal, and photolytic conditions. Validation studies for the in-house process impurities were performed for specificity, limit of detection (LOD), limit of quantitation (LOQ), linearity, precision, accuracy, and robustness. Thus, an improved RP-HPLC method capable of good separation of all known and unknown impurities with acceptable resolution and tailing factor was developed.http://dx.doi.org/10.1155/2020/3593805
spellingShingle Chaitali Kharat
Vaishali A. Shirsat
Yogita M. Kodgule
Mandar Kodgule
A Validated RP-HPLC Stability Method for the Estimation of Chlorthalidone and Its Process-Related Impurities in an API and Tablet Formulation
International Journal of Analytical Chemistry
title A Validated RP-HPLC Stability Method for the Estimation of Chlorthalidone and Its Process-Related Impurities in an API and Tablet Formulation
title_full A Validated RP-HPLC Stability Method for the Estimation of Chlorthalidone and Its Process-Related Impurities in an API and Tablet Formulation
title_fullStr A Validated RP-HPLC Stability Method for the Estimation of Chlorthalidone and Its Process-Related Impurities in an API and Tablet Formulation
title_full_unstemmed A Validated RP-HPLC Stability Method for the Estimation of Chlorthalidone and Its Process-Related Impurities in an API and Tablet Formulation
title_short A Validated RP-HPLC Stability Method for the Estimation of Chlorthalidone and Its Process-Related Impurities in an API and Tablet Formulation
title_sort validated rp hplc stability method for the estimation of chlorthalidone and its process related impurities in an api and tablet formulation
url http://dx.doi.org/10.1155/2020/3593805
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