LC-MS/MS法测定癫痫患者血浆中扑米酮的浓度

［摘要］〖HTH〗目的〖HTSS〗〖KG*2〗建立人血浆中测定扑米酮含量的高效液相色谱串联质谱（high performance liquid chromatography tandem mass spectrometry，LC-MS/MS）方法，并用于测定癫痫患者体内的血药浓度。〖HTH〗方法〖HTSS〗〖KG*2〗色谱柱：Phenomenex Kinetex XB-C18（50 mm×3 mm，2.6 μm）。流动相：甲醇（A）-2%甲酸水（B），进行梯度洗脱。流量：0.4 mL/min。柱温：40 ℃。进样量：5 μL。以咖啡因为内标，用电喷雾离子源进行正离子模式监测，多反应监测模式进行定量分析，源喷射电压5 500 V，离子源温度600 ℃。考察该方法的专属性、标准曲线及定量下限、精密度、回收率、稳定性及基质效应。选取20例临床口服扑米酮的癫痫患者（起始剂量为50 mg，1次/d；3 d后改为50 mg，2次/d；7 d后改为50 mg，3次/d；10 d后改为250 mg，3次/d），于2周后清晨取静脉血2 mL。用LC-MS/MS法测定扑米酮的血药浓度。〖HTH〗结果〖HTSS〗〖KG*2〗扑米酮在1~5 mg/L，最低定量下限为0.01 mg/L。平均回收率在95%以上，日间、日内精密度的相对标准偏差值均小于15%，稳定性良好。用该方法测定20例癫痫患者血样，其血药浓度范围为8.75~36.88 mg/L。〖HTH〗结论〖HTSS〗〖KG*2〗本法方便、快捷、专属性好、敏感度高、结果准确，可用于测定癫痫患者血浆中的扑米酮浓度。

Determination of primidone in plasma of epileptic patients by LC-MS/MS#br#

［Abstract］ Objective〖HTSS〗To establish a high performance liquid chromatography tandem mass spectrometry(LC-MS) method for the determination of primidone in human plasma and to apply it to the determination of plasma concentration in patients with epilepsy. 〖HTH〗〖WTHZ〗Methods〖HTSS〗Column: Phenomenex Kinetex XB-C18 （50 mm×3 mm，2.6 μm）. Mobile phase: methanol(A)-2% A acid water(B) for gradient elution. Flow rate: 0.4 mL/min. Column temperature:40 ℃. Sample volume: 5 μL. The internal standard was caffeine. The electrospray ion source was used for positive ion mode monitoring and the multi-reaction monitoring mode was used for quantitative analysis. The injection voltage of the source was 5 500 V and the temperature of the ion source was 600 ℃.The specificity, standard curve and lower limit of quantification, precision, recovery, stability and matrix effect of the method were investigated. Selection of 20 epileptic patients with oral primidone（the initial dose was 50 mg, 2 times a day after 3 days, 3 times a day after 1 week, 250 mg at the beginning of the 10 th day, 3 times a day),two weeks later, early in the morning, venous blood was taken for 2 mL. The plasma concentration of prochloramil was determined by LC-MS/MS. 〖HTH〗〖WTHZ〗Results〖HTSS〗The internal linear relationship of prometone was good between 1-5 mg/L, and the lowest quantitative lower limit is 0.01 mg/L. The average recovery was more than 95%, the relative standard deviation values of inter-day and intra-day precision were less than 15%, and the stability was good. The blood samples of 20 epileptic patients were determined by this method. The blood concentration range was 8.75-36.88 mg/L. 〖HTH〗〖WTHZ〗Conclusion〖HTSS〗This method is convenient, rapid, specific, sensitive and accurate. It can be used to determine the concentration of propranone in plasma of epileptic patients.