title: Simultaneous determination of piperaquine and its N-oxidated metabolite in rat plasma using LC-MS/MS.
abstract: A sensitive and efficient liquid chromatography tandem mass spectrometry method was developed and validated for the simultaneous determination of piperaquine (PQ) and its N-oxidated metabolite (PQ-M) in plasma. A simple protein precipitation procedure was used for sample preparation. Adequate chromatographic retention was achieved on a C18column under gradient elution with acetonitrile and 2 mm aqueous ammonium acetate containing 0.15% formic acid and 0.05% trifluoroacetic acid. A triple-quadrupole mass spectrometer equipped with an electrospray source was set up in the positive ion mode and multiple reaction monitoring mode. The method was linear in the range of 2.0-400.0 ng/mL for PQ and 1.0-50.0 ng/mL for PQ-M with suitable accuracy, precision and extraction recovery. The lower limits of detection (LLOD) were established at 0.4 and 0.2 ng/mL for PQ and PQ-M, respectively, using 40 μL of plasma sample. The matrix effect was negligible under the current conditions. No effect was found for co-administrated artemisinin drugs or hemolysis on the quantification of PQ and PQ-M. Stability testing showed that two analytes remained stable under all relevant analytical conditions. The validated method was successfully applied to a pharmacokinetic study performed in rats after a single oral administration of PQ (60 mg/kg).
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, Jinan, China.
authors.forename: Huixiang
authors.initials: H
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, Jinan, China.
authors.forename: Meitong
authors.initials: M
authors.lastname: Zang
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, Jinan, China.
authors.forename: Aijuan
authors.initials: A
authors.lastname: Yang
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, Jinan, China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Ji
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, Jinan, China.
authors.forename: Jie
authors.identifier: http://orcid.org/0000-0002-7911-9906
authors.initials: J
authors.lastname: Xing
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods; D004355:Drug Stability; D057230:Limit of Detection; D016014:Linear Models; D008297:Male; D011804:Quinolines / Q000097:blood* / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods; D010879:Piperazines
chemical_list: D011804:Quinolines; C034759:piperaquine; D010879:Piperazines
keywords: LC-ESI-MS/MS; metabolite; pharmacokinetics; piperaquine; rat plasma