Development And Application Of The Methods For The Quantification Of Propofol And Glipizide In Healthy Chinese Volunteers

The first part of this articleObjective:It is to determine the concentration of propofol in human plasma after intravenous infusion of propofol medium-chain triglyceride&long-chain triglyceride injection.Method:Chromatographic separation was achieved on an ACE Excel 3 Super C18column（2.1×50mm,3μm）with propofol-d17 as the internal standard,using a gradient elution with methanol and water containing 0.1%ammonia as the mobile phase.The detection was performed on a Triple Quad ^TM6500⁺mass spectrometer coupled with atmospheric pressure chemical ionization interface under negative ion multiple reaction monitoring（MRM）mode with the transition ion pairs of m/z 177.2→161.0 and m/z194.2→174.2 for propofol and its internal standard propofol-d17,respectively.Sample preparation was accomplished through simple one-step precipitation of plasma protein with acetonitrile.Results:The method was validated and proven to be reliable in human plasma in terms of selectivity,linearity,accuracy,precision,recovery,matrix effect,carryover and stability.The main pharmacokinetic parameters of propofol after administration of two different formulations.The 90%CIs of the ratios of the geometric means（test/reference）the main pharmacokinetic parameters obtained from the volunteers after administration of two different formulations were 86.44-104.88%for C_max,96.30-104.52%for AUC_0-tand 96.56-105.05%for AUC_0-∞,which were all within the predefined bioequivalence range of 80%-125%.Therefore,the two preparations were considered to be bioequivalent.Conclusion:The validated method was successfully applied to the bioequivalence study after single-dose intravenous administration of propofol medium-chain triglyceride&long-chain triglyceride injection in healthy Chinese subjects.The second part of the researchObjective:The aim of the second part of the research is to describe a rapid,simplified and sensitive high-performance liquid chromatography-electrospray ionization tandem mass spectrometry（HPLC-ESI-MS-MS）method.Methods:The method was described in this study for the determination of glipizide in human plasma employing glimepiride as the internal standard（IS）.Sample preparation was accomplished by one-step protein precipitation with acetonitrile,and chromatographic separation was performed on a Hedera ODS-2 column（2.1×150 mm,5μm）maintained at 30°C using a mobile phase of acetonitrile and ammonium acetate10 m M buffer containing 0.2%formic acid（55:45,v/v）.Mass spectrometric analysis was performed using an API 4000 triple quadrupole mass spectrometer coupled with an electrospray ionization source in positive ion mode.The multiple reaction monitoring mode of precursor-product ion transition at m/z 446.1→321.1 and m/z 491.1→352.1wasutilized to quantify glipizide and IS,respectively.Results:The method was proved to be precise and accurate at linearity concentration range of 3.164-843.8 ng/mL with correlation coefficients of more than 0.9990 for glipizide.The lower limit of quantification（LLOQ）was 3.164 ng/mL.The accuracy,precision,extraction recovery,matrix effects,and carryover effect of the validated method all met the acceptable limits.The main pharmacokinetic parameters obtained from the volunteers orally administered of glipizide controlled-release tablet（GCRT）were shown as follows:C_maxof 202.7±60.3 ng/mL occurred at 9.50±2.54 h.t_1/2was14.66±9.35 h,AUC_0-48hand AUC_0-∞were 3530±1203 and 4120±1272 ng/mL?h,respectively.Conclusion:The validated method with good sensitivity,rapid and accurate was successfully applied to investigate the pharmacokinetic profile of glipizide in 12 healthy Chinese subjects following single oral administration of glipizide controlled-release tablets.