Determination of raltegravir and raltegravir glucuronide in human plasma and urine by LC-MS/MS with application in a maternal-fetal pharmacokinetic study

Author(s)

Moreira, Fernanda de Lima ^[1] ; Marques, Maria Paula ^[1] ; Duarte, Geraldo ^[2] ; Lanchote, Vera Lucia ^[1]

Affiliation

^[1] Univ Sao Paulo, Dept Anal Clin Toxicol & Bromatol, Fac Ciencias Farmaceut Ribeirao Preto, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Obstet & Ginecol, Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Journal of Pharmaceutical and Biomedical Analysis; v. 177, JAN 1 2020.
• Web of Science Citations: 0

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 mu L plasma and 100 mu L 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 x 4.6 mm, 2.7 mu m) for both plasma and urine samples. The methods showed linearities at the ranges of 0.1-13.5 mu g/mL RAL and 0.15-19.5 mu g/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. (C) 2019 Published by Elsevier B.V. (AU)

• FAPESP's process: 18/05616-3 - Clinical pharmacokinetics in infectious diseases
• Grantee: Vera Lúcia Lanchote
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/23938-2 - Influence of pregnancy associated with HIV on the activity of OATP drug transporter in patients under treatment with Efavirenz
• Grantee: Fernanda de Lima Moreira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral