Open AccessDetermination of piperaquine concentration in human plasma and the correlation of capillary versus venous plasma concentrations
Author(s) -
Norah Mwebaza,
Vincent Cheah,
Camilla Forsman,
Richard Kajubi,
Florence Marzan,
Erika Wallender,
Grant Dorsey,
Philip J. Rosenthal,
Francesca Aweeka,
Liusheng Huang
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0233893
Subject(s) - piperaquine , dihydroartemisinin , chromatography , chemistry , pharmacokinetics , analyte , protein precipitation , liquid chromatography–mass spectrometry , venous blood , pharmacology , artemisinin , medicine , mass spectrometry , plasmodium falciparum , malaria , immunology
Background A considerable challenge in quantification of the antimalarial piperaquine in plasma is carryover of analyte signal between assays. Current intensive pharmacokinetic studies often rely on the merging of venous and capillary sampling. Drug levels in capillary plasma may be different from those in venous plasma, Thus, correlation between capillary and venous drug levels needs to be established. Methods Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was used to develop the method. Piperaquine was measured in 205 pairs of capillary and venous plasma samples collected simultaneously at ≥24hr post dose in children, pregnant women and non-pregnant women receiving dihydroartemisinin-piperaquine as malaria chemoprevention. Standard three-dose regimen over three days applied to all participants with three 40mg dihydroartemisinin/320mg PQ tablets per dose for adults and weight-based dose for children. Correlation analysis was performed using the program Stata® SE12.1. Linear regression models were built using concentrations or logarithm transformed concentrations and the final models were selected based on maximal coefficient of determination (R 2 ) and visual check. Results An LC-MS/MS method was developed and validated, utilizing methanol as a protein precipitation agent, a Gemini C 18 column (50x2.0mm, 5μm) eluted with basic mobile phase solvents (ammonium hydroxide as the additive), and ESI + as the ion source. This method had a calibration range of 10–1000 ng/mL and carryover was negligible. Correlation analysis revealed a linear relationship: C cap = 1.04×C ven +4.20 (R 2 = 0.832) without transformation of data, and lnC cap = 1.01×lnC ven +0.0125, (R 2 = 0.945) with natural logarithm transformation. The mean ratio (±SD) of C cap /C ven was 1.13±0.42, and median (IQR) was 1.08 (0.917, 1.33). Conclusions Capillary and venous plasma PQ measures are nearly identical overall, but not readily exchangeable due to large variation. Further correlation study accounting for disposition phases may be necessary.