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Naser L. Rezk
Talanta, Volume 85, Issue 4, September 2011
Abstract
The highly potent non-nucleoside reverse transcriptase inhibitor UC-781 is under development as a potential microbicide to prevent sexual transmission of human immunodeficiency virus type 1 (HIV-1). A sensitive and reproducible liquid chromatography–mass spectrometric method has been developed and validated for the quantification of the drug in New Zealand white rabbit plasma after liquid–liquid extraction procedure. The method was validated over the range of 1–500 ng mL−1. Average recoveries of the extraction method were high and consistent: 72%. The method is accurate with average accuracies over three QC (n = 30) concentrations ranging from 99.9% to 106.1%, and precise (within-day and between-day precision measures ranging from 2.2% to 9.9% and 6.50% to 9.0%, respectively). Plasma from other three species proved that extraction method did no affect analyte and internal standard stability. Due to its critical and consequential use, this assay could be readily used for investigational or clinical monitoring of plasma concentrations for low concentration as 1 ng mL−1 without interference.
Dr. Naser Rezk, PhD
Associate Professor
1-Eshelman School of Pharmacy, Division of Pharmacotherapy and Therapeutics, University of North Carolina at Chapel Hill, Chapel Hill, NC 2599, USA
2-King Abdullah International Medical Research Center, Riyadh, KSA
3-King Saud bin Abdelaziz Medical Sciences University, Riyadh, KSA
The non-nucleoside reverse transcriptase inhibitor UC781 is highly potent ARV agent. Topical vaginal microbicides represent successful option being evaluated to stop the spread of HIV. With drug candidates that have a specific action against HIV now being studied, it is important that, when appropriate and based on mechanism of action. The drug permeates into the vaginal tissue, vaginal secretion, and rectal tissue. Such topical microbisides drug agent is usually found in blood plasma in very low concentration. The analysis of UC781 in several species using LC-MS is crucial for developing the gel formation as well as to study the drug PK in many body compartments.
In many studies for using ARV’s as gel with different concentrations, microbicide proves to be highly effective in preventing HIV-1 transmission. Therefore accurate evaluation of drug concentration in biological fluids and tissue is necessary to study PK of systemic absorption of UC-781 in vaginal or rectal application. New Zealand white rabbit animal model is chosen to be first species. Then the assay applied as well on the rhesus macaque and finally to be utilized in human clinical study. The method is comparing SPE and liquid–liquid extraction. The final method relies initially on protein precipitation followed by liquid–liquid extraction.
UC781 is poor soluble in aqueous solution this make extraction from plasma or nay biological matrices is a challenging task. In this work we developed a novel sample preparation technique. That described technique was necessary to find an efficient extraction procedure for extracting the drug agent from the matrix in order to achieve accurate, specific and precise measurements.
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