title: A sensitive LC-MS/MS method for analysis of pericyazine in presence of 7-hydroxypericyazine and pericyazine sulphoxide in human plasma and its application to a comparative bioequivalence study in Chinese healthy volunteers.
abstract: A robust and highly sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of pericyazine in human plasma. The plasma sample was alkalized with sodium hydroxide solution and handled by liquid-liquid extraction with ethyl acetate after adding perphenazine as an internal standard (IS). The analytes were separated on an Ultimate™ AQ-C18 analytical column at 40°C, with a gradient elution consisting of A (aqueous phase: 5mM ammonium acetate buffer solution containing 0.1% formic acid) and B (organic phase: acetonitrile) at a flow rate of 0.350mL/min. The detection was conducted on an API 4000 tandem mass spectrometer coupled with electrospray ionization (ESI) source in positive ion mode. The multiple reaction monitoring (MRM) transitions, m/z 366.5>142.4 for pericyazine, m/z 382.5>142.4 for its 7-hydroxy and sulphoxide metabolites and m/z 404.3>171.3 for IS were chosen to achieve high selectivity in the simultaneous analyses. The method exhibited great improvement in sensitivity (LLOQ of 0.021ng/mL) and good linearity over the concentration range of 0.021-9.90ng/mL. The intra- and inter-day precision, accuracy, and stability results were within the acceptable limits and no matrix effect was observed. This method was successfully applied in a bioequivalence study to evaluate the pharmacokinetics in 20 healthy male Chinese volunteers. Additional exploratory analyses of 7-hydroxy and sulphoxide metabolites of pericyazine in the same samples suggest that the unchanged drug is predominant in the plasma and suitable for the bioequivalence comparison after a single oral administration of 10mg pericyazine.
authors.affiliation: Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha 410011, PR China; Institute of Clinical Pharmacy, Central South University, Changsha 410011, PR China.
authors.forename: Hua Lin
authors.initials: HL
authors.lastname: Cai
authors.affiliation: Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha 410011, PR China; Institute of Clinical Pharmacy, Central South University, Changsha 410011, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha 410011, PR China; Institute of Clinical Pharmacy, Central South University, Changsha 410011, PR China.
authors.forename: Ping Fei
authors.initials: PF
authors.lastname: Fang
authors.affiliation: Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha 410011, PR China; Institute of Clinical Pharmacy, Central South University, Changsha 410011, PR China.
authors.forename: SiSi
authors.initials: S
authors.lastname: Cao
authors.affiliation: Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha 410011, PR China; Institute of Clinical Pharmacy, Central South University, Changsha 410011, PR China.
authors.forename: Zhen Yan
authors.initials: ZY
authors.lastname: Hou
authors.affiliation: Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha 410011, PR China; Institute of Clinical Pharmacy, Central South University, Changsha 410011, PR China.
authors.forename: Yan Qin
authors.initials: YQ
authors.lastname: Wu
authors.affiliation: Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha 410011, PR China.
authors.forename: Xue Jiao
authors.initials: XJ
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha 410011, PR China; Institute of Clinical Pharmacy, Central South University, Changsha 410011, PR China. Electronic address: yan.miao@126.com.
authors.forename: Miao
authors.initials: M
authors.lastname: Yan
authors.affiliation: Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha 410011, PR China; Institute of Clinical Pharmacy, Central South University, Changsha 410011, PR China. Electronic address: bikui_zh@126.com.
authors.forename: BiKui
authors.initials: B
authors.lastname: Zhang
mesh_terms: D000328:Adult; D044466:Asian People; D002853:Chromatography, Liquid / Q000379:methods / Q000592:standards; D018592:Cross-Over Studies; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D010640:Phenothiazines / Q000032:analysis / Q000097:blood*; D013454:Sulfoxides / Q000032:analysis / Q000097:blood*; D053719:Tandem Mass Spectrometry / Q000379:methods / Q000592:standards*; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D010640:Phenothiazines; D013454:Sulfoxides; C084584:periciazine
keywords: 7-Hydroxypericyazine; Bioequivalence; LC–MS/MS; Pericyazine; Pericyazine sulphoxide