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

Abstract

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.

Review of Determination of Chlortalidone Levels in Pharmaceutical Preparations and Biological Matrix

“…Validation studies are carried out on impurities in the internal process to determine specificity, the limit of detection (LOD), the limit of quantification (LOQ), linearity, accuracy, precision, and reliability. Our improved RP-HPLC method is designed to separate all known and unknown impurities with acceptable resolution and tailing ratio [11]. They have developed high-performance liquid chromatography to simultaneously determine two ternary mixtures containing amiloride hydrochloride, atenolol, hydrochlorothiazide, and chlorthalidone to treat hypertension.…”

Mathematically Processed UV Spectroscopic Method for Quantification of Chlorthalidone and Azelnidipine in Bulk and Formulation: Evaluation of Greenness and Whiteness

“…e literature reported few analysis methods for quantification of CTL and AZE alone and in combination with other antihypertensive drugs. Several spectrophotometric methods [8][9][10][11][12][13][14], spectrofluorometric methods [8,13], HPLC [14][15][16], and HPTLC [17] methods were carried out for the estimation of CTL and AZE with other analytes in the formulations. Stability indicating RP-HPLC methods [18][19][20][21][22] were also reported in the literature for quantification of CTL and AZE separately.…”