Pharmacokinetic and bioequivalence study of Tenofovir Disoproxil Fumarate under fasting conditions on Argentine healthy-volunteers. Optimization and validation of SPE-LC-MS/MS for determination of Emtricitabine, Lamivudine and Tenofovir in human plasma

HUNZICKER GA; HEIN GJ; BALDO MN; HERNANDEZ SR; ALTAMIRANO JC

THE PHARMACEUTICAL AND CHEMICAL JOURNAL

TPCJ

Año: 2016 vol. 3 p. 157 - 168

2349-7092

Apharmacokinetic study based on single oral administration of Tenofovirdisoproxil fumarate 300 mg (tablets) to Argentinean male volunteers underfasting conditions is presented. The obtained values for test and referenceproducts were 238±62 and 261±73 ng mL-1 for Cmax; 1658±466 and 1801±529 ng mL-1 h for AUC0?48h; 1845±579 and 2015±639 ng mL-1 h for AUC0?∞, respectively. The 90% confidence intervals obtained by analysis of variancewere 85.0-97.2% for ln-Cmax, 87.2-97.9% for ln-AUC0?48h and 85.5-98.1% for ln-AUC0?∞, which are within the acceptance range of 80-125%.Both products were bioequivalent in terms of rate and extent of drug absorptionand therefore interchangeable. The analytical methodology was optimized andvalidated for determination of Emtricitabine (FTC), Lamivudine (3TC) and Tenofovir(TFV) in human plasma samples; which is the pharmaceutical combination mostcommonly used for treating HIV-infected patients. The analytical methodology wasbased on solid phase extraction (SPE) using Oasis® MCX mixed-mode cartridgescoupled to Liquid Chromatography and electrospray tandem mass spectrometry (LC-ESI-MS/MS).The analytical methodology was validated according to the US Food and DrugAdministration guidelines. Under optimized conditions, the analytical methodologylead to work within a clinical of 11-5434, 11-5452 and 13-397 ng mL-1 for FTC, 3TC and TFV, respectively; resulting widerthan others previously reported. The intra and inter batch precision (%RSD)across three validation runs was less than 14%. The accuracy determined at fourQC levels (LOQ, Low, Middle and High) was within 13%, in terms of percentrelative error.