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.

中文翻译：

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经验证的RP-HPLC稳定性方法，用于估计API和片剂中的氯噻酮及其与过程相关的杂质。

小剂量噻嗪类和类噻嗪类利尿剂被广泛用作高血压的一线治疗。高血压和充血性心力衰竭时经常开具氯磺酮（一磺胺基利尿药）。在这篇研究论文中，开发了一种改进的反相HPLC方法，用于同时鉴定和定量药典中和内部工艺中和降解相关的散装药物和制剂中氯噻酮的杂质。色谱分离在C ₈色谱柱（250×4.6 mm;'  5μm粒径），流速为1.4 mL / min，检测波长为220 nm。流动相A由比例为65:35（v / v）的缓冲溶液（正磷酸氢二铵（10 mM，pH 5.5））和甲醇组成，流动相B由比例为50:50的缓冲溶液和甲醇组成（ v / v）。API和制剂要经受压力条件，例如酸，碱，氧化，热和光解条件。对室内工艺杂质进行了验证研究，包括特异性，检测限（LOD），定量限（LOQ），线性，精度，准确性和鲁棒性。因此，开发了一种能够以可接受的分辨率和拖尾因子很好地分离所有已知和未知杂质的改进的RP-HPLC方法。