title: [Determination of decapeptide LXT-101 in plasma by HPLC-MS/MS and its pharmacokinetics in Beagle dogs].
abstract: This paper developed a sensitive and specific liquid chromatography-electrospray ionization mass spectrometry (HPLC-MS/MS) method for the determination of decapeptide LXT-101 in Beagle dog plasma. Plasma samples spiked with internal standard (IS) were treated with acetonitrile to precipitate the protein. Selected reaction monitoring (SRM) using the precursor --> product ion combinations of m/z 472.1-->587.9 and m/z 502.8-->633.8 were used to quantify LXT-101 and IS, respectively. The linear calibration curves were obtained in the concentration range of 0.5 - 500.0 ng x mL(-1). The limit of quantification (LOQ) was 0.5 ng x mL(-1). The inter-day and intra-day precision (RSD) across three validation run over the entire concentration range was below 10.9%, and the accuracy (RE) was within +/- 1.8%. The main pharmacokinetic parameters of LXT-101 after muscle injection of 20 microg x kg(-1) were as follows, AUC(0-t): (176.8 +/- 116.7) microg x h x L(-1), MRT(0-t): (2.52 +/- 0.53) h, T(1/2): (1.4 +/- 0.3) h; CL: (0.16 +/- 0.09) L x h(-1) x kg(-1), and Vd: (0.30 +/- 0.16) L x kg(-1), respectively. The method is proved to be specific, sensitive and suitable for the investigation of LXT-101 pharmacokinetics in Beagle dog.
authors.affiliation: Key Lab of Drug Metabolism and Pharmacokinetics, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China.
authors.forename: Ai-ying
authors.initials: AY
authors.lastname: Kong
authors.forename: Zhen-qing
authors.initials: ZQ
authors.lastname: Zhang
authors.forename: Jian-zhong
authors.initials: JZ
authors.lastname: Qiao
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Wen-xia
authors.initials: WX
authors.lastname: Zhou
authors.forename: Ke-liang
authors.initials: KL
authors.lastname: Liu
authors.forename: Jin-xiu
authors.initials: JX
authors.lastname: Ruan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D007273:Injections, Intramuscular; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000970:Antineoplastic Agents; C514029:LXT-101; D009842:Oligopeptides; D007987:Gonadotropin-Releasing Hormone