Quantifying the HIV-1 integrase inhibitor raltegravir in female genital tract secretions using high-performance liquid chromatography with ultraviolet detection

Abstract

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 218 nm. The method was linear from 0.05 to 10.0 mg/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.

Antiretroviral drug concentrations in the male and female genital tract: implications for the sexual transmission of HIV

“…In the last few years, excellent progress has been made in refining such methodologies [26][27][28] allowing for some detailed pharmacological studies to be performed on ART on the female genital tract. Pioneering work by Kashuba and colleagues has allowed great insight into patterns of ART drug disposition into the female genital tract [26,28,29 ,30 ,31-34].…”

Development and Validation of Extraction Method for the Determination of UC781 in Cervicovaginal Fluid

“…In that study we found large deference in CVF drugs penetration (from ≤10% to ≥100%) of blood plasma concentration [25]. Since then, we went over to the evaluation of many other ARV medications in FGT [4,26,27]. Most of these studies supported the usage of several ARV which could be an excellent pre-exposure/post-exposure prophylaxis (PrEP/PEP) candidate.…”

“…Methods to reduce or prevent sexual transmission of HIV-1 are urgently needed to sharply reduce the global HIV-1 epidemic [3]. Understanding the pharmacokinetics of drugs in human body compartments, such as the female genital tract, is especially important [4]. Among several classes of HIV inhibitors, many drugs belong to non-nucleoside reverse transcriptase inhibitors (NNRTIs).…”

Therapeutic Drug Monitoring of Antiretroviral Drugs in the Management of Human Immunodeficiency Virus Infection

“…Other studies of ARV drugs' PK include the analysis of seminal plasma in men [91,98], cervicovaginal fluid [99,100] and breast milk in women [101,102], and cerebrospinal fluid in both [103e105]. These TDM evaluations are primarily used to evaluate the distribution of ARV drugs into sanctuary sites in clinical studies aimed at the prevention of HIV transmission, and are not currently used for TDM of ART in clinical settings.…”