大鼠肺部给药后血浆中沙丁胺醇浓度的LC-MS/MS测定

Determination of Salbutamol in Rat Plasma after Pulmonary Administration by LC-MS/MS

建立了LC-MS／MS法测定大鼠血浆中沙丁胺醇浓度,并比较了两种沙丁胺醇气雾剂在大鼠体内的药动学行为。以特布他林为内标,血浆样品经乙酸乙酯液-液萃取。采用Capcell C18柱,流动相为乙腈-0．1％甲酸溶液(6:94),流速为0．25ml／min。质谱条件为串联四极杆质谱,电喷雾离子源,正离子扫描(ESI+);离子选择通道分别为240／148(沙丁胺醇)和226／152(内标)。沙丁胺醇线性范围为0．1～100ng／ml(r=0．9989),方法回收率为88．6％～107．4％;日内和日间RSD分别低于6．2％和7．3％。两种气雾剂在大鼠体内的药动学参数无显著性差异。

A LC-MS/MS method for determination of the concentration of salbutamol in rat plasma was established. In vivo pharmacokinetics of two brands of salbutamol aerosol in rats by pulmonary administration was investigated. Terbutaline was used as internal standard, and the samples were prepared by liquid-liquid extraction using ethyl acetate. A Capcell C18 column was used with the mobile phase of acetonitrile -0.1% formic acid （6： 94）, at a flow rate of 0.25ml/min. A tandem mass spectrometer equipped with electrospray ionization source was used as detector and was operated in the positive ion mode. Selected reaction monitoring using the precursor to product ion combinations of m/z 2401148 and 2261152 was performed to quantify salbutamol and the internal standard, respectively. The calibration curve of salbutamol was linear in the range of 0.1 - 100ng/ml （γ=0.9989）. The recovery was 88.6% - 107.4%. The RSDs of intra- and inter-day were lower than 6.2% and 7.3 %, respectively. In vivo pharmacokinetic parameters of two brands of salbutamol aerosol in rats had no significant difference.