Deng Pan, Duan Xiao-Tao, Chen Xiao-Yan, Li San-Ming, Zhong Da-Fang
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Yao Xue Xue Bao. 2008 Jan;43(1):76-80.
A liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method was developed for the determination of budesonide in dog plasma. Budesonide and the internal standard triamcinolone acetonide were separated from plasma by alkalinized liquid-liquid extraction with ethyl acetate. Chromatographic separation was performed on a Capcell Pak C18 MG column with the mobile phase consisted of acetonitrile -5 mmol x L(-1) ammonium acetate (60:40, v/v) at a flow-rate of 0.50 mL x min(-1). A tandem mass spectrometer equipped with electrospray ionization source was used as detector and operated in the negative ion mode. Quantification was performed using multiple reaction monitoring (MRM) of the transitions m/z 489 --> m/z 357 and m/z 493 --> m/z 413 for budesonide and the internal standard, respectively. The linear calibration curves were obtained in the concentration range of 25.0-2000 pg x mL(-1). The lower limit of quantification was 25.0 pg x mL(-1). The intra- and inter-day relative standard deviation over the entire concentration range was less than 15%. The accuracy was in the range of -8.1% to -1.7% in terms of relative error. The method was applied to a pharmacokinetic study of budesonide controlled-release capsules in Beagle dogs. Maximal budesonide plasma level was observed after (3.5 +/- 3.3) h and the Cmax was (786 +/- 498) pg x mL(-1) after a single oral administration of 9 mg budesonide capsules, Cmax was increased to (2142 +/- 1515) pg x mL(-1) after multiple oral administration (9 mg x 5 d) of budesonide capsules. This method was selective and rapid, and the sensitivity was sufficient for the purpose of the pharmacokinetic study of budesonide controlled-release formulation.
建立了一种液相色谱 - 串联质谱（LC-MS/MS）法测定犬血浆中的布地奈德。布地奈德和内标曲安奈德通过用乙酸乙酯进行碱化液 - 液萃取从血浆中分离出来。在Capcell Pak C18 MG柱上进行色谱分离，流动相为乙腈 - 5 mmol·L⁻¹醋酸铵（60:40，v/v），流速为0.50 mL·min⁻¹。配备电喷雾电离源的串联质谱仪用作检测器，在负离子模式下运行。分别使用布地奈德和内标的m/z 489→m/z 357和m/z 493→m/z 413的多反应监测（MRM）进行定量。在25.0 - 2000 pg·mL⁻¹浓度范围内获得线性校准曲线。定量下限为25.0 pg·mL⁻¹。在整个浓度范围内，日内和日间相对标准偏差均小于15%。相对误差方面，准确度在 - 8.1%至 - 1.7%范围内。该方法应用于比格犬布地奈德控释胶囊的药代动力学研究。单次口服9 mg布地奈德胶囊后，在（3.5±3.3）h观察到布地奈德血浆水平最高，Cmax为（786±498）pg·mL⁻¹，多次口服（9 mg×5 d）布地奈德胶囊后，Cmax增加到（2142±1515）pg·mL⁻¹。该方法具有选择性且快速，灵敏度足以用于布地奈德控释制剂的药代动力学研究。
