Akinloye, Abdulafeez, Eniayewu, Oluwasegun, Adeagbo, Babatunde, Bolaji, Oluseye and Olagunju, Adeniyi 
ORCID: 0000-0002-6588-5749
(2022)
Validation and Clinical Application of a Liquid Chromatography-Ultraviolet Detection Method to Quantify Dolutegravir in Dried Blood Spots.
THERAPEUTIC DRUG MONITORING, 44 (3).
pp. 430-437.
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2021 - Validation and Clinical Application of a Liquid Chromatography-Ultraviolet Detection Method to Quantify Dolutegravir in Dried Blood Spots.pdf - Author Accepted Manuscript Download (2MB) | Preview |
Abstract
<h4>Background</h4>Dolutegravir is currently the preferred component of first-line antiretroviral therapy. To facilitate clinical pharmacology studies in key populations, quantitative analytical methods compatible with microsampling and adaptable to resource-limited settings are desirable. The authors developed and validated a liquid chromatography-ultraviolet detection method to quantify dolutegravir in dried blood spots (DBS).<h4>Methods</h4>Calibration standards and quality control samples were prepared by spotting 50 μL of dolutegravir-spiked whole blood on each circle of DBS cards. Three spots (two 6-mm punches/spot) were extracted with methanol. Chromatographic separation was achieved with gradient elution of acetonitrile/potassium phosphate monobasic buffer (pH 5) on a reverse-phase C18 column (flow rate, 1 mL/min) using pioglitazone as the internal standard. UV detection was performed at 260 nm. In the clinical pharmacokinetic study, DBS from finger prick was collected from participants (n = 10) at 8 time points over 12 hours postdosing, with paired plasma at 1 and 12 hours. The method was used to quantify dolutegravir, estimating pharmacokinetic parameters. Agreement between DBS and plasma concentrations was evaluated using linearity and Bland-Altman plots.<h4>Results</h4>The method was validated over the concentration range of 0.4-10 mcg/mL, accuracy was 102.4%-114.8%, and precision was 3.4%-14.7%. The mean recovery was 42.3% (%CV: 8.3). The mean (±SD) dolutegravir concentration in DBS was 37.5% (±3.8%) lower than that in the plasma. DBS-derived and measured plasma concentrations showed strong correlation with linearity (R2 = 0.9804) and Bland-Altman plots. Means (%CV) of area under curve, Cmax, and C24 from the DBS-derived plasma concentration were 37.8 (23.2) mcg·h/mL, 2.7 (24.7) mcg/mL, and 1.34 (31.6) mcg/mL, respectively.<h4>Conclusions</h4>The application of this simple, accurate, and precise method will expand opportunities for clinical assessment of dolutegravir in resource-limited settings.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | dolutegravir, dried blood spot, pharmacokinetics, HPLC-UV, HIV |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 14 Oct 2021 14:38 |
| Last Modified: | 18 Jan 2023 21:27 |
| DOI: | 10.1097/FTD.0000000000000929 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3140396 |
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