高效液相色谱-串联质谱法测定犬血浆中盐酸二甲双胍浓度  

Determination of Metformin Hydrochloride in Dog Plasma by LC-MS/MS

作　　者：王慧[1] 邓杰[1] 易中宏[1] 张道林[1] 

机构地区：[1]重庆医药工业研究院有限责任公司,重庆400061

出　　处：《中国药师》2008年第11期1325-1327,共3页China Pharmacist

摘　　要：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 develop a sensitive and specific liquid chromatographic- tandem mass spectrometric （LC-MS/MS） method for determination of mefformin in clog plasma. Method ： The plasma samples were precipitated by aeetonitrile and the supernarant was injected onto LC-MS/MS system. The chromatographic system consisted of ZORBAX Eclipse XDB-Cls column （150 mm × 2. 1 mm, 3.5 μm） and the mobile phase consisted of 10 mmol.L^-1 ammonium buffer-aeetonitrile （50： 50） , flow rate was 0.3 ml.min^-1. A tandem mass spectrometer equipped with electrospray ionization （ESI） source was used as detector and operated in the positive ion mode. Multiple reaction monitoring （MRM） using the precursor→produet ion combinations of m/z 130-60 and m/z 304→182 were used to quantify mefformin and the internal standard, respectively. Result： The linear calibration curve was obtained in the concentration range of 2.0 - 4117 ng· ml^-1. The lower limit of quantification was 2.0 ng· ml^- 1. The intra-and inter-day precision （RSD） across three validation runs over the entire concentration range was less than 13%. The method was successfully applied in a pharmacokinetic study of mefformin in Beagle dog. Conclusion： The method is proved to be sensitive, rapid, and suitable for animal pharmaeokinetic investigation of metformin.

关 键 词：二甲双胍 液相色谱-串联质谱法 血浆药物浓度 

分 类 号：R969.1[医药卫生—药理学]