Quantifying the HIV-1 integrase inhibitor raltegravir in female genital tract secretions using high-performance liquid chromatography with ultraviolet detection.
Understanding the pharmacokinetics of drugs in peripheral body compartments, such as the genital tract, is particularly important in the infectious diseases arena. However, extracting drugs from small volumes of viscous, proteinacious substances like cervicovaginal fluid is particularly challenging. The goal of this study was to develop a method to quantify raltegravir, an HIV-1 integrase inhibitor, in the female genital tract. The method included sample preparation with perchloric acid followed by solid-phase extraction, separation with reverse-phase high-performance liquid chromatography, and detection with an ultraviolet wavelength of 218nm. The method was linear from 0.05 to 10.0mg/L, with minimal endogenous interference. The method was accurate (1.2-11.0% deviation) and precise (1.1-12.6% CV) for both within and between-day analyses. The ability to detect raltegravir in the female genital tract is essential for future investigations of raltegravir as an agent for prevention of HIV acquisition, and this method will be used for clinical studies further evaluating pharmacokinetic-pharmacodynamic relationships in this body compartment.
Talameh
Jasmine A
JA
Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill, Eshelman School of Pharmacy, Campus Box #7569, Chapel Hill, NC 27599, USA. jtalameh@email.unc.edu
Rezk
Naser L
NL
Kashuba
Angela D M
AD
D000284:Administration, Oral; D012634:Bodily Secretions / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D005836:Genitalia, Female / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000032:analysis*; D006801:Humans; D016014:Linear Models; D010472:Perchlorates; D011760:Pyrrolidinones / Q000032:analysis*; D000068898:Raltegravir Potassium; D052616:Solid Phase Extraction / Q000379:methods; D013048:Specimen Handling / Q000379:methods; D013056:Spectrophotometry, Ultraviolet
D019428:HIV Integrase Inhibitors; D010472:Perchlorates; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium