Joshua Gini1,2, Sujan Dilly Penchala1,2, Alieu Amara1,2, Elizabeth Challenger1,2, Deirdre Egan1,2, Catriona Waitt1,3, Mohammed Lamorde3, Catherine Orrell4, Landon Myer5, Saye Khoo1,2, Laura J Else1,2. 1. Department of Molecular & Clinical Pharmacology, University of Liverpool, 70 Pembroke Place, Liverpool, L69 3GF, UK. 2. Liverpool Bioanalytical Facility, Royal Liverpool Hospital, Prescot Street, Liverpool, L7 8XP, UK. 3. Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda. 4. Desmond Tutu HIV Foundation, Gugulethu Community Health Centre, Cape Town, South Africa. 5. Centre for Infectious Diseases Epidemiology & Research, University of Cape Town, South Africa.
Abstract
AIM: 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. Results/methodology: 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 C18 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. CONCLUSION: 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.
AIM: 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. Results/methodology: 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 C18 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. CONCLUSION: 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.
Entities:
Keywords:
HIV; antiretroviral; breast milk; clinical trial; dolutegravir; mass spectrometry; pharmacokinetics; validation
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