Analytical advances in the quantitative and qualitative determination of clonidine and methyldopa: A review

Clonidine and methyldopa are centrally acting antihypertensive agents that lower blood pressure by stimulating α₂-adrenoceptors in the brain stem, thereby reducing sympathetic outflow. While clonidine hydrochloride is widely used in resistant hypertension, hypertensive crises, and pediatric attention-deficit hyperactivity disorder (ADHD), methyldopa remains the preferred agent for pregnancy-induced hypertension. Reliable quantification of these drugs in pharmaceutical formulations and biological matrices is essential for quality control, therapeutic monitoring, and evaluations of parameters of pharmacokinetics. This review critically summarizes analytical methodologies applied to clonidine and methyldopa, encompassing spectrophotometric, fluorometric, electrochemical, chromatographic (HPLC, LC-MS, GC-MS), and advanced hyphenated techniques. Key performance parameters-sensitivity, selectivity, linearity, and detection limits-are compared, with emphasis on the predominance of HPLC methods for clonidine and spectrophotometric assays for methyldopa. Despite significant progress, challenges remain in developing rapid, cost-effective, and highly selective methods suitable for complex biological matrices and high-throughput applications. By consolidating available data, this review provides a comprehensive yet focused reference for researchers, pharmaceutical analysts, and clinicians seeking reliable strategies for the estimation of these two centrally acting α₂-agonists.