Work

Quantification of dolutegravir, bictegravir, raltegravir and doravirine in human breastmilk with UPLC-MS/MS

Year: 2025

Type: article

Abstract: With the use of newer and more robust antiretrovirals, the risk of viral transmission through breastfeeding has sharply diminished. This has led to a change in guideline recommendations. Currently, breastfeeding is regarded as a equipoise of formula, in case of a well-controlled HIV infection. However, it is not yet fully established whether infant exposure to antiretroviral drugs through breastmilk is a reason for concern. To accurately describe infant exposure of antiretrovirals through breastmilk, reproducible bioanalytical methods are needed.Our existing UPLC-MS/MS method for several anti-HIV drugs in EDTA-plasma was modified for validation of dolutegravir, bictegravir, raltegravir and doravirine concentrations in human breastmilk. [13C,2H5]-Dolutegravir, [13C,2H2,15N]-bictegravir, [2H6]-raltegravir and [13C6]-doravirine were used as internal standard. The sample preparation involved protein precipitation and detection was performed with tandem mass spectrometry (MS/MS) in a total runtime of 10 minutes.The assay was validated over the concentration range of 0.0100 – 10.0 mg/L for dolutegravir and doravirine, 0.00500 – 10.0 mg/L for raltegravir and 0.0200 – 20.0 mg/L for bictegravir. Within-run and between-run accuracy were within ±10% of the nominal concentration and precision <10 CV% for quality controls at high, medium and low concentrations, and ±8.8% and <14 CV%, respectively, at the lower limit of quantification for all analytes. Extraction recovery was 125% and 122% for dolutegravir and its internal standard, 114% and 115% for bictegravir and its internal standard, 144% and 149% for raltegravir and its internal standard and 103% and 100% for doravirine and its internal standard. Processed samples of dolutegravir, bictegravir, raltegravir and doravirine in breastmilk were 108%, 95.5%, 105% and 102% after 14 days at 4oC.The assay is currently being implemented successfully in pharmacokinetic studies.

Source: Journal of Chromatography B

DOI: 10.1016/j.jchromb.2025.124739

Authors: L.C. van der Wekken - Pas, E.W.J. van Ewijk - Beneken Kolmer, L.H.M. te Brake, D.M. Burger

Institutions: Radboud University Nijmegen, Radboud University Medical Center

Language: English

Topic: Analytical Methods in Pharmaceuticals

Subfield: Analytical Chemistry

Field: Chemistry

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,640