中国临床药理学杂志2018，Vol.34Issue(1)：53-56,4.DOI:10.13699/j.cnki.1001-6821.2018.01.014
HPLC-MS/MS法同时测定人血清中利培酮与帕利哌酮及奥氮平和喹硫平的浓度
Simultaneous determination the concentration of risperidone, paliperidone,olanzapine and quetiapine in human serum by HPLC-MS/MS
摘要
Abstract
Objective To develop a simultaneous determination method of risperidone,paliperidone,olanzapine and quetiapine in human serum for therapeutic drug monitoring.Methods Clinical serum samples were prepared by protein precipitation and analytes were determined using HPLC-MS/MS.An Eclipse XDB C1s column (4.6 mm ×50 mm,1.8μm) was combined with mobile phase consisted of methanol,water and acetrile (37.5:12.5:50,plus 2.5 mmol · L-1 ammonium formate).The flow rate was 0.5 mL · min-1 The column temperature was 35 ℃ and the injection volume was 2 μL.MS detection was carried out using an electrospray ionization source operated in multiple reaction monitoring (MRM) mode.The ion transitions were m/z 427.3 → m/z 207.2(paliperidone),m/z 431.3--m/z 211.2 (paliperidone-D4),m/z 411→m/z 191 (risperidone),m/z 415.4→m/z195.2 (risperidone-D4),m/z 384.3→m/z 253.1 (quetiapine),m/z 392.3→m/z 258 (quetiapine-D8),m/z313→m/z 256 (olanzapine),m/z 316→m/z 256 (olanzapine-D3),respectively.Results The calibration curves of risperidone and paliperidone were y =0.67x +4.94 × 10-4 (R2 =0.999 4) and y =0.68x +0.14 × 10-2 (R2 =0.999 6),with the linear ranges of 1-100 ng · mL-1.The linear ranges were 2-200 ng · mL-1(calibration curve:y =1.33x-0.65 × 10-2,R2 =0.998 6) for olanzapine and 8-800 ng· mL-1 (calibration curve:y =1.80x-2.08 × 10-2,R2 =0.999 4) for quetiapine.The inter and intra-batch precisions of risperidone,paliperidone,olanzapine and quetiapine were all within 15 ％ in lower limit of quantitation (LLOQ),low,middle and high levels of quality control samples.The extraction efficiency was more than 90％ for four analytes.The concentration of analytes in quality control samples were less than ± 15 ％ bias compared with nominal concentration after storage at room temperature for 24 h,-70 ℃ for 34 d or after freeze-thaw for 3 cycles.Conclusion The validated method was simple,fast and sensitive for the simultaneous determination of risperidone,paliperidone,olanzapine and quetiapine in human serum.The method was applied to the therapeutic drug monitoring for patients administered with the above drugs.The stability of mixed quality control samples is reliable and can be used for therapeutic drug monitoring.关键词
高效液相色谱串联质谱/治疗药物监测/抗精神病药物Key words
HPLC-MS/MS/therapeutic drug monitoring/antipsychotics分类
医药卫生引用本文复制引用
倪晓佳,王占璋,卢浩扬,尚德为,温预关..HPLC-MS/MS法同时测定人血清中利培酮与帕利哌酮及奥氮平和喹硫平的浓度[J].中国临床药理学杂志,2018,34(1):53-56,4.基金项目
广东省自然科学基金资助项目(2015A030313808) （2015A030313808）
广州市医学重点学科建设基金资助项目 （）
广州市医药卫生科技基金资助项目(20171A011267) （20171A011267）
