Posaconazole: A Triazole Antifungal Drug: Estimation of Chiral Isomers Using a Chiral Chromatography

Abstract

Posaconazole is a second-generation triazole antifungal agent widely used in the prevention and treatment of invasive fungal infections, particularly in immune-compromised patients. The complex molecular architecture of Posaconazole, characterized by a triazole ring, difluorophenyl moiety, tetrahydrofuran ring, and a piperazine group, is designed to optimize antifungal activity, pharmacokinetics, and bioavailability. Crucially, it contains four chiral centers, giving rise to up to 16 (2⁴) stereoisomers, among which only one is therapeutically active. This study emphasizes the necessity of chiral purity analysis due to the profound impact of stereochemistry on drug safety, efficacy, and metabolism. The current study deals with the development and validation of a simple, robust chiral HPLC method using a Chiralpak IB-3 column with a chiral selector of Cellulose tris (3,5-dimethylphenylcarbamate) and dimensions of 250 mm × 4.6 mm, 3 μm of particle size. A 5:25:61:9:0.1 v/v/v/v/v ratio of ethanol, isopropyl alcohol, n-hexane, dichloromethane, and diethanolamine is used as a mobile phase for the quantification of chiral isomers. The method demonstrates strong performance in terms of system suitability, specificity, sensitivity, linearity, accuracy, precision, robustness, and solution stability. This work provides a critical analytical tool for quality control and regulatory compliance and underscores the broader importance of stereoisomeric evaluation in pharmaceutical development.