关键词:  丙泊酚, 糖基化, 注射剂, 药代动力学, 葡萄糖

Abstract:

Objective：To estimate the pharmacokinetics for two solution types of propofol glycoside injections in rats. Methods: A high performance liquid chromatography-high resolution mass spectrometry (HPLC-MS) was established for measuring propofol in rat plasma. Two kinds of propofol glycoside injections were developed and intravenously administered to rats via tail vein, respectively, and a commercially available propofol emulsion injection was intravenously administered as a control. Propofol plasma concentration-time curves were determined, and the pharmacokinetic parameters were estimated. Results: HPLC-MS measurement was performed by using a quadrupole-orbit trap high-resolution mass spectrometer on a C18 chromatographic column. The mobile phase consisted of water and methanol (20∶80, V/V). The ion source was an atmospheric pressure chemical ion source, and the negative ion was used for detection with a scanning mode of selective ion monitoring in which m/z 177.127 4 was used for propofol and m/z 149.096 1 used for thymol as an internal standard. A linear correlation between concentration and peak area ratio was constructed in the range of 50 μg/L-10.0 mg/L propofol. The limit of quantification was 50 μg/L propofol. The average recoveries of propofol from plasma were in the range of 93.6%-101.1%, and intraday or inter-day relative standard deviation for measurement was <14%. The pharmacokinetic results showed that the two kinds of propofol glycoside injections exhibited the same pharmacokinetic behavior. However, the clearance and area under curve values of propofol for the two propofol glycoside injections were evidently increased as compared with those for propofol emulsion injection, respectively. Furthermore, their apparent distribution volumes were increased as well. Nevertheless, the propofol elimination half-life (t1/2) value of the newly developed propofol glycoside injections was the same as that of commercial propofol emulsion injection (approximately 1.5 h).Conclusion: The established HPLC-MS method can be used for measuring propofol concentration accurately in rat plasma. The clearance and distribution volumes of propofol glycoside injection are bigger than those of the propofol emulsion injection.

Key words: Propofol, Glycosylation, Injection, Pharmacokinetics, Glucose