White Analytical Perspective on Lamivudine Determination: HPLC-PDA and HPLC-ELSD Method Development, Validation, and Multimetric Evaluation.

Lamivudine (LMV) is a nucleoside reverse transcriptase inhibitor widely used in the treatment of HIV and hepatitis B infections. This study aimed to develop and validate rapid, accurate, and ecofriendly HPLC methods for the quantitative analysis of LMV in pharmaceutical formulations using photodiode array (PDA) and evaporative light scattering detector (ELSD) systems. Chromatographic separation was achieved on a C18 column (250 mm × 4.6 mm, 5 μm) using an isocratic mobile phase of ethanol-water (7:93, v/v) at a flow rate of 1.0 mL min-1. The developed methods were validated according to ICH Q2-(R2) guidelines in terms of specificity, linearity, precision, accuracy, sensitivity, and robustness. Environmental and practical sustainability were further assessed using AGREE, AGREEprep, AES, MoGAPI, SPMS, RAPI, BAGI, and CACI tools within the framework of White Analytical Chemistry (WAC). Both methods exhibited excellent linearity, with correlation coefficients (R2) of 0.9995 (PDA) and 0.9976 (ELSD). LOD and LOQ values were 0.12-0.40 μg mL-1 and 3.25-10.82 μg mL-1, respectively. Recovery results ranged between 98.56 and 101.42% with RSD values <2%. The AGREE, AES, and MoGAPI scores (0.72-0.69, 86-87, and 80-82%, respectively) confirmed high greenness, while BAGI (70-72.5) and CACI (73-78) values indicated strong applicability and practicality. Although the HPLC-ELSD method showed slightly lower whiteness due to its higher LOQ and energy consumption, both proposed methods demonstrated acceptable analytical performance, applicability, and environmental compatibility. The developed approaches thus provide sustainable, reliable, and cost-effective analytical platforms consistent with the principles of WAC.