LC-MS法测定全血中酪丝亮肽及其在大鼠中的药代动力学研究

Determination of Tyroserleutide in Blood by LC-MS and the Pharmacokinetics Study in Rats

建立准确、灵敏的液相色谱-质谱法以测定全血中酪丝亮肽,并研究酪丝亮肽静脉注射后在大鼠中的药代动力学。大鼠麻醉,进行颈动脉插管,静脉注射酪丝亮肽(200μg/kg、400μg/kg和800μg/kg),采集血样。样品处理后,以YSW肽为内标,采用正离子选择性反应监测,乙腈-水-甲酸系统洗脱,测定全血中酪丝亮肽的浓度,并计算药动学参数。酪丝亮肽在大鼠中被快速降解,半衰期极短,约为20s。该研究的LC-MS法准确、灵敏、结果可靠;酪丝亮肽静脉注射给药半衰期极短,临床中不宜采用静脉注射给药,建议探索新的给药方案。

To establish an accurate and sensitive LC-MS method for determination of Tyroserleutide in rats＇ blood, and to investigate the pharmacokinetics of Tyroserleutide after intravenous injection in rats. The rats were anaesthetized and the cannula was inserted into the carotid artery. Tyroserleutide was administrated to rats by Tyr-ser-Len intravenous injection with the dose of 200 μg/kg, 400μg/kg and 800 μg/kg, then the blood Samples were collected. After disposals of the samples, the concentration of Tyroserleutide was determined by LC- MS method with positive ion SIM detection, using YSW as internal standard, and the CHCH3CN--H2O--H3COOH as elution system. The pharmacokinetics parameters were calculated. The Tyroserleutide was rapidly degraded, with a short half life （about 20s）. The LC- MS method has proved to be accurate and sensitive, and the results are reliable. The Tyroserleutide has a short half life after bolus intravenous injection. The dosage regimen is not suggested in clinical trial and another new regimen needs to be further investigated.