Comparison of lopinavir and ritonavir drug concentrations in plasma and dried blood spots (DBS) in HIV infected patients in Thailand

Name: Yardpiroon Tawon

keyword: Lopinavir

; Ritonavir

; Dried blood spots

; LC-MS/MS

; HIV infections

; Antiretroviral drugs

Abstract: Lopinavir/ritonavir (LPV/RTV) remains a commonly administered HIV protease inhibitor in HIV-infected patients in Thailand. Lopinavir is a HIV protease inhibitor administered with low dose ritonavir to enhance its bioavailability. Antiretroviral drug measurement can be useful for the clinical management of patients with drug toxicities, drug-drug interactions, as well as optimization of dosing for pregnant women and young children. Drug measurements are performed using plasma samples and they require storage and shipping under frozen conditions. Dried blood spots (DBS) is an alternative sample matrix for drug measurement as they can be stored at room temperature and shipped in the normal post. A new liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS) assay was developed and validated to quantify lopinavir and ritonavir from DBS. Sample preparation involved a liquid-liquid extraction. Chromatographic separation was performed on a Gemini Polar Reversed Phase C18 column (150 x 2.0 mm ID, 5µm) using a stepwise gradient. The calibration curve was linear over the range 0.05 to 20 µg/mL. The lower limit of quantification was 0.05 µg/mL. The assay average accuracy was 102-112% for lopinavir and 90-112% for ritonavir. The assay precision (inter- and intra assay) expressed as coefficient of variation (%CV) was <6% for lopinavir and <9.0% for ritonavir. The recoveries for lopinavir and ritonavir were 82.1% and 102.6%, respectively. Both drugs were stable in DBS stored at room temperature for at least 3 months. Sample hematocrit (30-60%) had no effect. Concentrations of lopinavir and ritonavir in paired plasma and DBS samples collected from 155 HIV-infected patients (median age 29 years, range 3 to 70), during 0.1-17 hours after the last dose and the hematocrit of samples ranged from 28.1 to 48.2%. Plasma and DBS concentrations for lopinavir and ritonavir were highly correlated (Pearson correlation r = 0.964 and r =0.990, respectively). The Bland-Altman plot indicated no proportional bias between the DBS and plasma assays (p>0.05). However, lopinavir and ritonavir concentrations were 29.3% and 24.6% lower in DBS than in plasma, respectively. In conclusion, the LC-MS/MS assay validated for the quantification of lopinavir and ritonavir in DBS is robust, accurate and precise. Lopinavir and ritonavir concentrations in DBS are lower than plasma. Current target antiretroviral drug concentrations are based on plasma concentration thresholds, therefore drug concentrations determined from DBS samples need to be adjusted to estimate the plasma concentrations before interpretation

Thammasat University. Thammasat University Library

Address: BANGKOK

Email: preserv@tu.ac.th

Name: Tullayakron Plengsuriyakarn

Role: advisor

Name: Kesara Na Bangchang

Role: co-advisor

Name: Cressey, Timothy

Role: co-advisor

Created: 2015

Modified: 2021-10-12

Issued: 2021-10-12

วิทยานิพนธ์/Thesis

application/pdf

DOI: 10.14457/TU.the.2015.310

eng

DegreeName: Master of Science

Level: Master's Degree

Descipline: Bioclinical Sciences

Grantor: Thammasat University

©copyrights Thammasat University

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