[Determination of decapeptide LXT-101 in plasma by HPLC-MS/MS and its pharmacokinetics in Beagle dogs].
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.
Kong
Ai-ying
AY
Key Lab of Drug Metabolism and Pharmacokinetics, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China.
Zhang
Zhen-qing
ZQ
Qiao
Jian-zhong
JZ
Zhang
Fan
F
Zhou
Wen-xia
WX
Liu
Ke-liang
KL
Ruan
Jin-xiu
JX
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
D000970:Antineoplastic Agents; C514029:LXT-101; D009842:Oligopeptides; D007987:Gonadotropin-Releasing Hormone