Validation and Clinical Application of a Novel LC-MS Method for Quantification of Dolutegravir in Breast Milk

Overview

Journal Bioanalysis

Specialty Chemistry

Date 2018 Nov 20

PMID 30450920

Citations 3

Authors

Joshua Gini

Sujan Dilly Penchala

Alieu Amara

Elizabeth Challenger

Deirdre Egan

Catriona Waitt

Mohammed Lamorde

Catherine Orrell

Landon Myer

Saye Khoo

Laura J Else

Affiliations

Soon will be listed here.

Abstract

A novel, sensitive and reproducible method for quantification of dolutegravir (DTG) in dried breast milk spots (DBMS) was developed and validated for use in clinical studies. Its application enabled measurement of DTG pharmacokinetics in breastfeeding mothers and their infants. Sample extraction was by liquid-liquid extraction using tert-butyl methy-ether, with DTG-d5 as an internal standard. DTG was eluted on a reverse phase C Waters XBridge (3.5 μm: 2.1 × 50 mm) column using a gradient mobile phase consisting of 0.1% formic acid in deionised water or methanol. The assay was validated over a calibration range of 10-4000 ng/ml. Stability, inter and intra-assay variability were acceptable according to FDA and EMA bioanalytical method guidelines. The assay is robust, accurate, precise and can be reliably applied for analysis of clinical samples in trials from low resource settings.

Citing Articles

Rapid and sensitive liquid chromatographic-tandem mass spectrometric methods for the quantitation of dolutegravir in human plasma and breast milk.

Rackow A, Pandey A, Price A, Marzinke M J Mass Spectrom Adv Clin Lab. 2024; 34:1-7.

PMID: 39429949 PMC: 11488435. DOI: 10.1016/j.jmsacl.2024.09.001.

Optimizing Pharmacology Studies in Pregnant and Lactating Women Using Lessons From HIV: A Consensus Statement.

Eke A, Olagunju A, Momper J, Penazzato M, Abrams E, Best B Clin Pharmacol Ther. 2020; 110(1):36-48.

PMID: 32930408 PMC: 8167886. DOI: 10.1002/cpt.2048.

Safety and pharmacokinetics of dolutegravir in pregnant mothers with HIV infection and their neonates: A randomised trial (DolPHIN-1 study).

Waitt C, Orrell C, Walimbwa S, Singh Y, Kintu K, Simmons B PLoS Med. 2019; 16(9):e1002895.

PMID: 31539371 PMC: 6754125. DOI: 10.1371/journal.pmed.1002895.

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