Determination of Metroprolol in Rat Plasma after Acute Hydrogen Sulfide Poisoning by Liquid chromatography-mass Spectrometry

作者：Chen Xiaole; Wang Li; Chen Lianguo; Wang Shuanghu; Xu Tao; Sun Wei; Li Junwei; Pan Jianchun; Wang Xianqin; Hu Guoxin^*

来源：Latin American Journal of Pharmacy, 2012, 31(8): 1143-1148.

• CYP 2D6
• LC-MS
• Hydrogen sulfide poisoning
• Metroprolol
• Plasma

A sensitive and selective liquid chromatography-mass spectrometry (LC-MS) method for determination of metroprolol in rat plasma was developed and validated. After addition of carbamazepine as internal standard (IS), protein precipitation by acetonitrile was used as sample preparation. The chromatographic separation was performed on a Zorbax SB-C18 column (150 x 2.1 mm, 5 mu m), using acetonitrile-0.1 % formic acid as the mobile phase with gradient elution, delivered at a flow rate of 0.4 mL/min. Electrospray ionization (ESI) source was applied and operated in positive ion mode, and selected ion monitoring (SIM) mode used to quantify metroprolol. Calibration curves were linear in the concentration ranges of 5-2000 ng/mL for metroprolol, with a lower limit of quantification (LLOQ) of 5 ng/mL. Intraand inter-day precision were less than 12 % and the accuracy ranged from -6.3 % to 4.9 %. The validated method was used to study the pharmacokinetic profile of metroprolol in rat plasma after acute hydrogen sulfide poisoning on I. V. metroprolol sodium for intravenous administration. The main pharmacokinetic parameters of metroprolol was significantly different in hydrogen sulfide exposured rats. The t(1/2) and AUC(0-infinity) of metroprolol increased significantly and CLz decreased markedly after acute hydrogen sulfide poisoning. The findings of this study suggest that acute hydrogen sulfide poisoning tended to inhibit CYP2D6.

• 出版日期2012
• 单位司法部司法鉴定科学技术研究所; 温州医科大学