1. Determination of raltegravir and raltegravir glucuronide in human plasma and urine by LC-MS/MS with application in a maternal-fetal pharmacokinetic study.
- Author
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Moreira FL, Marques MP, Duarte G, and Lanchote VL
- Subjects
- Brazil, Chromatography, High Pressure Liquid methods, Female, Glucuronides administration & dosage, Glucuronides blood, Glucuronides chemistry, HIV Infections blood, HIV Infections urine, HIV Integrase Inhibitors administration & dosage, HIV Integrase Inhibitors chemistry, HIV Integrase Inhibitors pharmacokinetics, Humans, Infant, Newborn, Permeability, Placenta metabolism, Pregnancy, Pregnancy Complications, Infectious blood, Pregnancy Complications, Infectious urine, Pregnancy Trimester, Third metabolism, Raltegravir Potassium administration & dosage, Raltegravir Potassium chemistry, Raltegravir Potassium pharmacokinetics, Tandem Mass Spectrometry methods, Umbilical Cord chemistry, HIV Infections drug therapy, HIV Integrase Inhibitors analysis, Maternal-Fetal Exchange, Pregnancy Complications, Infectious drug therapy, Raltegravir Potassium analysis
- Abstract
Raltegravir (RAL) is a HIV-integrase inhibitor recommended for treatment of HIV type 1 infection during pregnancy. The elimination of RAL to RAL glucuronide (RAL GLU) is mediated primarily by UDP glucuronosyltransferase 1A1 (UGT1A1). The present study shows the development and validation of 4 different methods for the analysis of RAL and RAL GLU in plasma and in urine samples. The methods were applied to evaluate the maternal-fetal pharmacokinetics of RAL and RAL GLU in a HIV-infected pregnant woman receiving RAL 400 mg twice daily. The sample preparation for RAL and RAL GLU analysis in 25 μL plasma and 100 μL diluted urine (10-fold with water containing 0.1% formic acid) were carried out by protein precipitation procedure. RAL and RAL GLU generate similar product mass fragments and require separation in the chromatographic system, so a suitable resolution was achieved for unchanged RAL and RAL GLU employing Ascentis Express C18 (75 × 4.6 mm, 2.7 μm) for both plasma and urine samples. The methods showed linearities at the ranges of 0.1-13.5 μg/mL RAL and 0.15-19.5 μg/mL RAL GLU in urine and 10-2000 ng/mL RAL and 2.5-800 RAL GLU in plasma. Precise and accurate evaluation showed coefficients of variation and relative errors ≤ 15%. The methods have been successfully applied in a maternal-fetal pharmacokinetic study., (Copyright © 2019. Published by Elsevier B.V.)
- Published
- 2020
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