Validation and Clinical Application of a Liquid Chromatography-Ultraviolet Detection Method to Quantify Dolutegravir in Dried Blood Spots

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dc.contributor.authorAkinloye, Abdulafeez
dc.contributor.authorEniayewu, Oluwasegun
dc.contributor.authorAdeagbo, Babatunde
dc.contributor.authorOluseye, Bolaji
dc.contributor.authorOlagunju, Adeniyi
dc.date.accessioned2023-05-17T09:54:06Z
dc.date.available2023-05-17T09:54:06Z
dc.date.issued2022-06-01
dc.description.abstractBackground 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). Methods 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 h post-dosing, with paired plasma at 1 and 12 h. The method was used to quantify dolutegravir, estimating pharmacokinetic parameters. Agreement between DBS and plasma concentrations was evaluated using linearity and Bland-Altman plots. Results The method was validated over the concentration range of 0.4-10 μg/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 (±standard deviation) 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 AUC, Cmax, and C24 from the DBS-derived plasma concentration were 37.8 (23.2) μg.h/mL, 2.7 (24.7) μg/mL and 1.34 (31.6) μg/mL, respectively. Conclusions The application of this simple, accurate, and precise method will expand opportunities for clinical assessment of dolutegravir in resource-limited settings.en_US
dc.description.sponsorshipWe acknowledge the infrastructural support from the Translational Pharmacokinetic Research Laboratory, Obafemi Awolowo University. This study was supported by a Wellcome Trust International Fellowship to Adeniyi Olagunju, Ph.D. (204776/Z/16/Z and 204776/A/16/Z). The HPLC-UV system was supported by an EDCTP Career Development Fellowship to Babatunde Adeagbo, Ph.D. (TMA2017CDF-1860). The funders played no role in the conduct of this study, including study design, sample collection, data analysis, preparation, and publication.en_US
dc.identifier.other10.1097/FTD.0000000000000929
dc.identifier.urihttps://uilspace.unilorin.edu.ng/handle/20.500.12484/10317
dc.language.isoenen_US
dc.publisherLippincott Williams and Wilkinsen_US
dc.subjectDolutegraviren_US
dc.subjectDried blood spoten_US
dc.subjectPharmacokineticsen_US
dc.subjectHPLC-UVen_US
dc.subjectHIVen_US
dc.titleValidation and Clinical Application of a Liquid Chromatography-Ultraviolet Detection Method to Quantify Dolutegravir in Dried Blood Spotsen_US
dc.typeArticleen_US

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