目的：建立LC-M S/M S测定人血浆中肌苷浓度的方法并应用于异丙肌苷药代动力学研究。方法以阿德福韦为内标，采用甲醇∶10 mmol/L 乙酸铵（15∶85，v/v ）为流动相，以Agilent SB-C18柱（5μm粒径，150．0 mm ×4．6 mm I ．D ．）为分析柱，通过电喷雾电离源（ESI），M RM扫描方式进行检测。用于定量分析的离子反应分别为m/z母离子为267．3，子离子为135．0（肌苷）和m/z母离子为272．0，子离子为134．1（阿德福韦）。结果血浆中肌苷定量的线性范围10～3000 ng/m L ，定量下限为10 ng/mL。日内、日间精密度（RSD）小于5％，平均回收率大于90％，无基质效应。结论本法专属性强，样品处理方便，灵敏度高，适用于肌苷临床药动学研究。
A rapid and sensitive liquid chromatography-tandem mass spectrometry（LC-MS/MS） method for the de- termination of cefotetan in human plasma was developed and validated. After the protein precipitation of sample with acetonitrile, the analyte and internal standard（IS）, tramadol, were separated on a Zorbax XDB C8 column using ace- tonitrile/1%（volume fraction） formic acid（volume ratio 35：65, pH=2.5） as mobile phase at a flow rate of 1.0 mL/min with a 1 ： 1 split. The detection was performed by electrospray ionization with positive ion mode, followed by multiple reaction monitoring of the transitions for cefotetan at m/z 576.3→460.2（quantifier） and m/z 576.3→432.2（qualifier） and for IS at m/z 264.1→58.1. Cefotetan and IS were eluted at 1.86 and 1.87 rain, respectively. The assay was linear over the concentration range of 0.1-100 gg/mL for 20 μL of human plasma only with intra- and inter-day preci- sions（expressed as the relative standard deviation） of less than 6.62% and accuracies（as relative error） of ＋1.31%. The method was applied to the pharmacokinetic study of a l-h intravenous infusion of 1.0 g of cefotetan disodium for human volunteers（n=6）.
SHI MeiyunYIN LeiCAI LanlanWANG CanLIU XidongZHAO SenSUN YantongFAWCETT J. PaulZHAO LimeiYANG YanGU Jingkai
A rapid and sensitive method based on liquid chromatographtandem mass spectrometry （LC-MS/MS） for the determination of a novel anticoagulant peptide bivalirudin in human plasma has been developed and validated. Plasma samples were precipitated protein with acetonitrile and reextracted with dichloromethane, after which the analyte and triptorelin as an internal standard （IS） were separated on a 300SB-Cl8 column （150 mm x 4.6 mm i.d., 5 gm particle size） using 0.1% formic acid：methanol （45：55, v/v） as mobile phase. The triple-quadrupole mass spectrometer, equipped with electrospray ionization （ESI） interface, was operated in the positive ion mode, and the multiplereaction monitoring （MRM） transitions of bivalirudin and IS were at m/z 1091.0-650.4 and m/z656.5 - 249.3, respectively. The lower limit of quantification （LLOQ） was 1 ng/mL for 100 ng/mL plasma sample and the assay was linear over the concentration range 1 1000 ng/mL. The accuracy was within a range from -0.4% to 0.5% in terms of relative error （RE） and the intra- and inter-day precisions in terms of relative standard deviation （RSD） were 〈2.92 and 〈 3.36, respectively. The method was successfully applied to a pharmacokinetic study involving intravenous administration of bivalirudin （0.5 mg/kg） to Chinese volunteers.
