Novel fluorometric determination of lenacapavir using orange-emitting carbon dots: A sensitive method for therapeutic drug monitoring in HIV treatment

초록

Lenacapavir (LEN), a first-in-class HIV capsid inhibitor, requires precise analytical methods for therapeutic drug monitoring and pharmacokinetic studies. This study presents the first fluorometric method for LEN detection utilizing orange-emitting carbon dots (O-CDs). The method exploits the inner filter effect mechanism, where LEN's UV absorption at 270 nm overlaps with the O-CDs' excitation spectrum, resulting in concentration-dependent fluorescence quenching. The method demonstrated excellent linearity (2.0–50.0 ng/mL, R2 = 0.9959) with a limit of detection of 0.92 ng/mL in plasma. High recovery rates of 95.4–97.0 % were achieved in rat plasma samples with RSD values below 5 %. Method selectivity was ensured through mixed-mode strong anion-exchange solid-phase extraction. Clinical relevance was validated through successful application to rat plasma pharmacokinetic studies in both healthy and renal-impaired animals. The method accurately determined pharmacokinetic parameters and distinguished significant alterations between groups. This fluorescence-based method offers a practical, sensitive alternative to conventional chromatographic approaches for LEN quantification, supporting therapeutic drug monitoring and research applications.

키워드