HPLC-MS/MS法测定血浆中十肽化合物LXT-101及Beagle犬药代动力学研究  

Determination of decapeptide LXT-101 in plasma by HPLC-MS/MS and its pharmacokinetics in Beagle dogs

作　　者：孔爱英[1] 张振清[1] 乔建忠[1] 张帆[1] 周文霞[1] 刘克良[1] 阮金秀[1] 

机构地区：[1]军事医学科学院毒物药物研究所药代动力学重点实验室,北京100850

出　　处：《药学学报》2008年第9期946-950,共5页Acta Pharmaceutica Sinica

基　　金：国家高技术研究发展计划(863计划)资助项目(2002AA2Z3121)

摘　　要：建立HPLC—MS／MS法测定血浆中十肽化合物（LXT-101）的浓度，并应用于Beagle犬的药代动力学研究。血浆样品采用乙腈直接沉淀蛋白的方法，内标（IS）选用^127I-LXT-101，采用ESI—MS／MS二极质谱，选择反应监测（SRM）方式进行检测。LXT-101的线性范围为0．5—500．0ng·mL^1（r^2〉0．9930），绝对回收率为85．2％-90．7％，日内、日间精密度（RSD％）均小于10．9％，准确度（RE）在±1．8％之内。血浆中的最低检测限（LOQ）为0．5ng·mL^-1。该法操作简便、快速、灵敏度高。可检测出低剂量肌注（im）给药后犬体内的血药浓度，适于临床前药代动力学研究。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 · mL^-1. The limit of quantification （LOQ） was 0. 5 ng · 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 μg · kg^-1 were as follows, AUC0-t; （176.8±116.7） μg·h · L^-1, MRT0-t; （2.52±0.53） h, T1/2： （1.4±0.3） h; CL： （0. 16±0.09） L· h^-1 · kg^-1, and Vd： （0.30 ±0. 16） L · kg^-1, respectively. The method is proved to be specific, sensitive and suitable for the investigation of LXT-101 pharmacokinetics in Beagle dog.

关 键 词：十肽 HPLC—MS/MS 药代动力学 

分 类 号：R917[医药卫生—药物分析学] R969.13[医药卫生—药学]