论文部分内容阅读
目的:建立测定犬血浆中二甲双胍浓度的高效液相色谱-质谱-质谱联用方法,并用于二甲双胍缓释片非临床药物动力学研究。方法:血浆样品经乙腈沉淀蛋白,取上清液直接进行LC-MS/MS测定,以10 mmol·L~(-1)甲酸铵缓冲液-乙腈(50:50)为流动相,采用ZORBAX Eclipse XDB-C_(18)柱(150 mm×2.1 mm,3.5μm)分离,在三级四极杆串联质谱中经电喷雾电离源(ESI)离子化,以多反应监测(MRM)方式进行检测。用于定量分析的离子反应分别为m/z 130→60(二甲双胍)和m/z 304→182(可卡因,内标)。结果:LC-MS/MS法测定血浆中二甲双胍的线性范围为2.0～4117 ng·ml~(-1),定量下限为2.0 ng·ml~(-1)。以3个浓度水平的质量控制样品求得各浓度水平日内、日间精密度(RSD)均小于13%。在非临床药代动力学研究中,应用此法测定了受试Beagle犬血浆中二甲双胍的浓度。结论:该法灵敏、快速、操作简便,适用于二甲双胍的动物药物动力学研究。
Objective: To establish a method for the determination of metformin in canine plasma by high performance liquid chromatography-mass spectrometry-mass spectrometry (LC-MS / MS) and to study the non-clinical pharmacokinetics of metformin sustained-release tablets. Methods: The plasma samples were precipitated by acetonitrile, and the supernatant was used for LC-MS / MS determination. The mobile phase consisted of 10 mmol·L -1 ammonium formate-acetonitrile (50:50) XDB-C_ (18) columns (150 mm × 2.1 mm, 3.5 μm) were separated and electrospray ionization (ESI) ionization in triple quadrupole tandem mass spectrometry. Multiple reaction monitoring (MRM) The ion reactions used for quantitative analysis were m / z 130 → 60 (metformin) and m / z 304 → 182 (cocaine, internal standard), respectively. Results: The linear range of LC-MS / MS for the determination of metformin in plasma was 2.0-4117 ng · ml -1 and the lower limit of quantitation was 2.0 ng · ml -1. The results showed that the intra-day and inter-day precision (RSD) were less than 13% for the quality control samples at three concentration levels. In non-clinical pharmacokinetic studies, this method was used to determine the plasma concentration of metformin in Beagle dogs. Conclusion: The method is sensitive, rapid and easy to operate. It is suitable for animal pharmacokinetics study of metformin.