title: Improved liquid chromatography-tandem mass spectrometry method for the analysis of eptifibatide in human plasma.
abstract: A rapid, selective and highly sensitive high performance liquid chromatography-tandem mass spectrometry method (LC-MS/MS) was developed and validated for the determination and pharmacokinetic investigation of eptifibatide in human plasma. Eptifibatide and the internal standard (IS), EPM-05, were extracted from plasma samples using solid phase extraction. Chromatographic separation was performed on a C(18) column at a flow rate of 0.5 mL/min. Detection of eptifibatide and the IS was achieved by tandem mass spectrometry with an electrospray ionization (ESI) interface in positive ion mode. Traditional multiple reaction monitoring (MRM) using the transition of m/z 832.6-->m/z 646.4 and m/z 931.6-->m/z 159.4 was performed to quantify eptifibatide and the IS, respectively. The calibration curves were linear over the range of 1-1000 ng/mL with the lower limit of quantitation validated at 1 ng/mL. The intra- and inter-day precisions were within 13.3%, while the accuracy was within +/-7.6% of nominal values. The validated LC-MS/MS method was successfully applied for the evaluation of pharmacokinetic parameters of eptifibatide after intravenous (i.v.) administration of a 45 microg/kg bolus of eptifibatide to 8 healthy volunteers.
authors.affiliation: Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
authors.forename: Zhi-Ling
authors.initials: ZL
authors.lastname: Zhou
authors.forename: Xi-Yong
authors.initials: XY
authors.lastname: Yu
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Mai
authors.forename: Qiu-Xiong
authors.initials: QX
authors.lastname: Lin
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Deng
authors.forename: Zhi-Xin
authors.initials: ZX
authors.lastname: Shan
authors.forename: Su-Juan
authors.initials: SJ
authors.lastname: Kuang
authors.forename: Ping
authors.initials: P
authors.lastname: Zhu
authors.forename: Xiao-Zhong
authors.initials: XZ
authors.lastname: Huang
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Li
authors.forename: Tie-Feng
authors.initials: TF
authors.lastname: Chen
authors.forename: Shu-Guang
authors.initials: SG
authors.lastname: Lin
mesh_terms: D044466:Asian People; D002853:Chromatography, Liquid; D004355:Drug Stability; D000077542:Eptifibatide; D005260:Female; D006262:Health; D006801:Humans; D008297:Male; D010455:Peptides / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D010975:Platelet Aggregation Inhibitors / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D012015:Reference Standards; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013997:Time Factors
chemical_list: D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D000077542:Eptifibatide