【摘要】 本文研究硝碘酚腈注射液在鄂尔多斯细毛羊体内的动力学特征，为临床合理用药提供依据。随机选取9只3～4周岁、体重相近、临床健康的鄂尔多斯细毛羊，按10 mg·kg^-1颈部皮下注射硝碘酚腈，按照事先设定好的16个不同时间点采集血液并分离血浆。血浆样品采用液液萃取结合固相萃取进行预处理，借助液相色谱-串联质谱（LC-MS/MS）法测定样品中的硝碘酚腈动态浓度，并利用Phoenix WinNolin 7.0软件处理血药浓度数据。硝碘酚腈在浓度25.00～2 000.00 ng·mL^-1范围内线性关系良好（R²=0.999 7），定量下限为25.00 ng·mL^-1，硝碘酚腈和内标的提取回收率均高于84%，日内、日间的RSD均小于3%，满足药代动力学研究的方法学要求。羊皮下注射硝碘酚腈注射液(10 mg·kg^-1)后，在羊体内吸收良好，达峰时间(T_max)约为（15.56±6.46）h，达峰浓度(C_max)约为（31.74±1.73）μg·mL^-1，药时曲线下面积（AUC）为（17 563.71±2 188.05）h·μg·mL^-1，半衰期(T_1/2)为（250.66±50.44）h，平均驻留时间（MRT）为（431.06±34.80）h，表观分布容积（Vd）为（201.32±40.52）mL·kg^-1。本研究成功建立了硝碘酚腈血药浓度的LC-MS/MS测定方法，并发现硝碘酚腈注射液在鄂尔多斯细毛羊体内吸收良好、消除缓慢、平均驻留时间长、组织分布广、药效维持时间长。更多还原

【Abstract】 This paper aimed to study the kinetic characteristics of Nitroxynil injection in Ordos fine-wool sheep, providing a basis for clinical rational use of drugs. 9 ordos fine-wool sheep（3-4 years old, clinically healthy, and with similar body weight） were randomly selected. The Nitroxynil was subcutaneously injected into the neck at 10 mg·kg^-1, and blood samples were collected at 16 pre-set time following drug administration, then the plasma was separated. Samples were pretreated via the hexane delipidation followed by the solid phase extraction, and the plasma concentration of Nitroxynil was determined by liquid chromatography-tandem mass spectrometry（LC-MS/MS）. Data were analyzed by using the software of Phoenix WinNolin 7. 0. The quantification method was validated, giving a limit of quantification（LOQ） of 25. 00 ng·mL^-1, a good linearity between 25. 00 and 2 000. 00 ng·mL^-1（R²=0. 999 7）, and an extraction recovery（Nitroxynil and 13C6 Nitroxynil） of more than 84%. Both inter and intra-day precision（RSD）were lower than 3%, which met the methodological requirements of pharmacokinetic research. The time to maximum plasma concentration(T_max) was（15. 56±6. 46）h, and maximum concentration(C_max) was（31. 74±1. 73）μg·mL^-1, the area under the Concentration-time curve（AUC） was（17 563. 71±2 188. 05）h·μg·mL^-1, the half-life(T_1/2) was（250. 66±50. 44）h, the mean residence time（MRT） was（431. 06±34. 80）h, and the apparent volume distribution was（201. 32±40. 52）mL·kg^-1, respectively. The LC-MS/MS method for determining the Nitroxynil concentration in sheep plasma was successfully established, and the Nitroxynil injection was well absorbed and distributed, with a long mean retention time and effective period in Ordos fine-wool sheep.更多还原