Determination of The Antimalarial Drug Piperaquine in Small Volume Pediatric Plasma Samples by LC–MS/MS

Abstract

Aim Determination of piperaquine (PQ) in pediatric plasma requires a method with a small sample volume. Results We report a sensitive LC–MS/MS method for quantitation of PQ with only 25 µI human plasma. Using a deuterated internal standard (PQ-d6), an analytical PFP column, APCI+ as the ion source and MRM (535/288 for PQ and 541/294 for the IS) for detection, the method has a linear calibration range of 1.5–250 ng/ml with a runtime of 3.0 min per sample. The method was applied to plasma samples from children. Conclusion The developed LC–MS/MS method is suitable for pediatric studies with small volume plasma samples collected via capillary tubes. One limitation was the performance of PFP columns varied among different brands.

Simultaneous determination of piperaquine and its N‐oxidated metabolite in rat plasma using LC‐MS/MS

“…Electrospray ionization produced the precursor ion [M + H] + for all analytes in positive mode, and the most abundant and characteristic fragment ions were selected in the MRM transitions of PQ, PQ‐M and IS (Figure ). Atmospheric‐pressure chemical ionization (APCI) had an advantage over ESI in a previous pharmacokinetic study on piperaquine (Kjellin et al ., ). In the present study, APCI led to lower matrix effect for PQ, but not for its metabolite PQ‐M.…”

Metabolite identification of the antimalarial piperaquine in vivo using liquid chromatography–high‐resolution mass spectrometry in combination with multiple data‐mining tools in tandem

“…PQ is a weak base with multiple p K a values, and it is very hydrophilic at low pH and very lipophilic at high pH (log P 6.2; Kjellin et al , ; Lindegardh et al , ). Using water containing 0.2% formic acid as mobile phase A and acetonitrile as mobile phase B, symmetric chromatographic peaks were obtained for PQ and its metabolites in this study (Figs ).…”

“…To improve the extraction efficiency, the solid‐phase extraction columns were eluted with 0.5 mL of acetonitrile–water (9:1 v /v) containing 0.2% formic acid, which was used to lower the pH to protonate PQ. PQ has been reported to adsorb readily to glass surfaces (Tarning and Lindegardh, ; Kjellin et al , ), and plastic material was therefore used throughout the analytical process.…”

“…Oxidation of a methylene group on the piperazine ring leading to the corresponding keto‐piperazine or ring‐opening of piperazine has been described in previous studies, such as trimetazidine (Jackson et al , ) and a psychoactive substance methoxypiperamide (Meyer et al , ). In addition, PQ and its major metabolites could show multiple chromatographic peaks with similar MS/MS profiles owing to their multiple p K a values (Kjellin et al , ; Lindegardh et al , ).…”

Metabolite identification of the antimalarial naphthoquine using liquid chromatography–tandem high‐resolution mass spectrometry in combination with multiple data‐mining tools

“…The structure of NQ is similar to piperaquine (PQ), belonging to 4-amino quinoline. Based on previous reports, PQ is absorb readily to glass surfaces (Kjellin, Dorsey, Rosenthal, Aweeka, & Huang, 2014;Tarning et al, 2008), thus plastic materials were used throughout the analytical process.…”