Emerging Analytical Strategies for Screening Hydrochlorothiazide in Fixed Dose Combinations: A Comprehensive Review

Hydrochlorothiazide (HCTZ) is one of the most widely prescribed thiazide diuretics which is frequently formulated in fixed-dose combinations with angiotensin II receptor blockers, Angiotensin Converting Enzyme (ACE) inhibitors, calcium channel blockers and other anti-hypertensive agents. The extensive clinical use of these combinations necessitates reliable analytical methods for their simultaneous estimation in pharmaceutical dosage forms and biological matrices. The purpose of this study is comprehensively examine previously reported chromatographic and hyphenated analytical methods for HCTZ analysis in combinations with other drugs. The Published literature outlining the analytical techniques for HCTZ based combination dosage forms and its applications were reviewed. Stability indicating Reverse Phase High Performance Liquid Chromatography (RP-HPLC) method remains the most commonly employed techniques for routine quality control and stability testing due to their simplicity, robustness, and regulatory compliances. LC-MS/MS method provides superior sensitive and selective making them suitable for bioanalytical applications such as pharmacokinetics and bioequivalence studies. High Performance Thin Layer Chromatography (HPTLC) offers a cost-effective alternative for pharmaceutical analysis. Recent studies increasingly apply Analytical Quality by Design (AQbD) principles to enhance method optimization. Emerging applications includes impurity profiling, mixed mode chromatography and analysis of novel dosage forms. A reviewed analytical method for HCTZ based fixed dose combination drugs demonstrates excellent accuracy, precision and sensitivity supporting their suitability for reliable pharmaceutical quality control and bioanalytical evaluation. Continuous advancement in chromatographic techniques and AQbD based approaches further strengthen the analytical framework for HCTZ combination drugs.