Determination of tulobuterol in rat plasma using a liquid chromatography-tandem mass spectrometry method and its application to a pharmacokinetic study of tulobuterol patch

作者：Han, Xiao; Liu, Ran; Ji, Lifang; Hui, Mei; Li, Qing; Fang, Liang; Bi, Kaishun^*

来源：Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences, 2016, 1008: 108-114.

DOI：10.1016/j.jchromb.2015.11.017

• Tulobuterol patch
• LC-MS/MS
• Transdermal administration
• Linear pharmacokinetic study

A sensitive and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for determination of tulobuterol in rat plasma for the first time. Plasma samples were extracted by liquid-liquid extraction method with methyl tert-butyl ether and the analyte and clenbuterol (IS) were separated on a Venusil MP C-18 column (100mm x 2.1 mm, 3 mu m) using 0.1% formic acid-water-methanol as mobile phase, with a runtime of 5 min. The analyte was detected in multiple reaction monitoring (MRM) mode with positive electrospray ionization. Transitions of m/z 228.2 -> 154.0 for tulobuterol and m/z 277.1 -> 203.0 for the clenbuterol were monitored. The linear range was 0.5-100 ng/ml (r = 0.9967) for tulobuterol with the lower limit of quantitation of 0.5 ng/ml. The intra-day and inter-day precisions were less than 10.3% for the analyte and the accuracy was less than -8.6%. The RSD of matrix effect and recovery yield were within +/- 15% of nominal concentrations and tulobuterol was stable during stability studies. The validated method has been successfully applied to a pharmacokinetic study of three doses of tulobuterol patch in rats for the first time.

• 出版日期2016-1-1
• 单位沈阳药科大学