高效液相色谱-串联质谱方法测定血清中氨磺必利、舒必利、米那普仑、西酞普兰、文拉法辛及O-去甲文拉法辛浓度
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摘要
目的:建立人血清中氨磺必利、舒必利、米那普仑、西酞普兰、文拉法辛及O-去甲文拉法辛浓度同时测定的LC-MS/MS方法,实现临床样本的血药浓度监测。方法:以去甲基氨磺必利和D,L-N,N-二去甲文拉法辛为内标,甲醇-乙腈溶剂沉淀蛋白;使用ES Sonoma C_(18)(2)色谱柱(50 mm×2.1 mm,3μm)以甲醇和6 mmol·L~(-1)乙酸铵水溶液为流动相,梯度洗脱;使用三重四级杆进行检测,采用电喷雾的离子源,在正离子模式下以MRM的扫描模式进行定量分析。结果:方法经验证,空白基质的干扰小,注射完高浓度样品后在空白样品中的残留符合要求,高浓度样品可以稀释2倍后进行分析,基质因子变异系数RSD小于15%,处理后的样品12 h内分析稳定、未处理样本4℃冰箱存放1周稳定,氨磺必利在15.53～497.00 ng·mL~(-1)、舒必利在18.03～577.00 ng·mL~(-1)、米那普仑在7.91～253.05 ng·mL~(-1)、西酞普兰在9.71～310.62 ng·mL~(-1)、文拉法辛在8.62～275.83 ng·mL~(-1)、O-去甲文拉法辛在9.19～293.92 ng·mL~(-1)范围内均具有良好的线性关系(R~2>0.99),方法的准确度高、精密度好。结论:该方法的样本处理简单,样本分析时间短,可以实现大量临床样本的快速分析,已成功应用于临床服用氨磺必利、舒必利、米那普仑、西酞普兰或文拉法辛的患者的血药浓度监测。
OBJECTIVE To establish a LC-MS/MS method for the simultaneous measurement of amisulpride, sulpiride, milnacipran, citalopram, venlafaxine and O-desvenlafaxine in human serum and to monitor the plasma concentration of clinical samples. METHODS The analytes were extracted by protein precipitation using desmethyl amisulpride and D,L-N,N-didesmethyl venlafaxine as internal standard. The separation was achieved on ES Sonoma C_(18)(2) column(50 mm×2.1 mm, 3 μm) with gradient eluted program using methanol and 6 mmol·L~(-1 )ammonium acetate as mobile phase. API4000 triple quadrupole system equipped with an electrospray ionization ion-trap source(ESI) was used as the detector and operated in the positive ion mode. Analytes were detected in the multiple reaction(MRM) monitoring mode. RESULTS The method verified that the interference of blank matrix was minor,and the residue of high concentration sample in blank sample met the requirements after injection. The high concentration sample could be diluted twice for analysis. The coefficient of variation(RSD) of matrix factor was less than 15% and the treated sample could remain stable within 12 h, while the untreated sample could remain stable in refrigerator at 4 ℃ for 1 week. A good linear relationship was observed with amisulpride in the range of 15.53-497.00 ng·mL~(-1) and sulpiride in the range of 18.03-577.00 ng·mL~(-1), milnacipran in the range of 7.91-253.05 ng·mL~(-1), citalopram in the range of 9.71-310.62 ng·mL~(-1), venlafaxine in the range of 8.62-275.83 ng·mL~(-1), and O-desvenlafaxine in the range of 9.19-293.92 ng·mL~(-1)(R~2>0.99). The accuracy and precision of the method were good. CONCLUSION The method is simple, rapid and has been successfully applied to monitor the blood concentration of patients who were administered amisulpride, sulpiride, milnacipran, citalopram or venlafaxine.
OBJECTIVE To establish a LC-MS/MS method for the simultaneous measurement of amisulpride, sulpiride, milnacipran, citalopram, venlafaxine and O-desvenlafaxine in human serum and to monitor the plasma concentration of clinical samples. METHODS The analytes were extracted by protein precipitation using desmethyl amisulpride and D,L-N,N-didesmethyl venlafaxine as internal standard. The separation was achieved on ES Sonoma C_(18)(2) column(50 mm×2.1 mm, 3 μm) with gradient eluted program using methanol and 6 mmol·L~(-1 )ammonium acetate as mobile phase. API4000 triple quadrupole system equipped with an electrospray ionization ion-trap source(ESI) was used as the detector and operated in the positive ion mode. Analytes were detected in the multiple reaction(MRM) monitoring mode. RESULTS The method verified that the interference of blank matrix was minor,and the residue of high concentration sample in blank sample met the requirements after injection. The high concentration sample could be diluted twice for analysis. The coefficient of variation(RSD) of matrix factor was less than 15% and the treated sample could remain stable within 12 h, while the untreated sample could remain stable in refrigerator at 4 ℃ for 1 week. A good linear relationship was observed with amisulpride in the range of 15.53-497.00 ng·mL~(-1) and sulpiride in the range of 18.03-577.00 ng·mL~(-1), milnacipran in the range of 7.91-253.05 ng·mL~(-1), citalopram in the range of 9.71-310.62 ng·mL~(-1), venlafaxine in the range of 8.62-275.83 ng·mL~(-1), and O-desvenlafaxine in the range of 9.19-293.92 ng·mL~(-1)(R~2>0.99). The accuracy and precision of the method were good. CONCLUSION The method is simple, rapid and has been successfully applied to monitor the blood concentration of patients who were administered amisulpride, sulpiride, milnacipran, citalopram or venlafaxine.
引文
[1] Hiemke C,Baumann P,Bergemann N,et al.AGNP consensus guidelines for therapeutic drug monitoring in psychiatry:Update 2011 [J].Pharmacopsychiatry,2011,44(6):195-235.
[2] Hiemke C,Baumann P,Bergemann N,et al.AGNP consensus guidelines for therapeutic drug monitoring in psychiatry:Update 2011 [J].Practical Pharma Clin Remedies(实用药物与临床),2016,19(10):1193-1218.
[3] Taubel J,Ferber G,Fox G,et al.Thorough QT study of the effect of intravenous amisulpride on QTc interval in caucasian and japanese healthy subjects [J].Br J Clin Pharmacol,2017,83(2):339-348.
[4] Sparshatt A,Taylor D,Patel MX,et al.Amisulpride - dose,plasma concentration,occupancy and response:Implications for therapeutic drug monitoring [J].Acta Psychiatr Scand,2009,120(6):416-428.
[5] Liu FZ,Hu ZF,Wang JH.A study on the relationship between clinical efficacy of sulpiride and serum concentration [J].Shandong Arch Psychiatry(山东精神医学),2003,16(1):26-27.
[6] Chen ML,Song LS,Gao ZS,et al.The relationship between sulpiride plasma concentration and its adverse effect [J].Shanghai Archives of Psychiatry(上海精神医学),1998,10(3):161-162.
[7] Wille SM,Cooreman SG,Neels HM,et al.Relevant issues in the monitoring and the toxicology of antidepressants [J].Crit Rev Clin Lab Sci,2008,45(1):25-89.
[8] CSLM.The development and management suggestion of laboratory developed tests in china [J].Chin J Lab Med(中华检验医学杂志),2017,40(3):162-164.
[9] Ch.P.Vol Ⅰ(中国药典.一部)[S].2015:363.
[10] Wang ST,Li Y.Development of aUPLC-MS/MS method for routine therapeutic drug monitoring of aripiprazole,amisulpride,olanzapine,paliperidone and ziprasidone with a discussion of their therapeutic reference ranges for chinese patients [J].Biomed Chromatogr:BMC,2017,31(8).
[11] Tang Y,Yu Q,Nan F,et al.Simultaneous quantitative determination of rotundine and sulpiride in human plasma with liquid chromatography-tandem mass spectrometry [J].J Chin Mass Spectrometry Society(质谱学报),2008,29(1):13-17.
[12] Zhao LR,Zhao H,Liu H,et al.Determination of levosulpiride in human plasma and the application in pharmacokinetics by LC-MS/MS[J].J Shenyang Pharmaceutical Univ(沈阳药科大学学报),2015,32(4):304-310.
[13] Chen XY,Hao GT,Zhang YF,et al.Determination of milnacipran in human plasma by HPLC-MS/MS [J].Chin J Clin Pharmacol(中国临床药理学杂志),2016,32(7):643-645.
[14] Qiu PY,Mai JW,Liang ZX,et al.Determination of escitalopram in human plasma by HPLC-MS/MS [J].J Guangdong Pharmaceutical Univ(广东药科大学学报),2015,31(4):432-436.
[15] Li L,Li H,Xiang YC,et al.Simultaneous determination of four antidepressants in human plasma by LC-MS/MS [J].Chin J Clin Pharm(中国临床药学杂志),2016,25(6):339-344.
[16] Liu GR,Qiao S,Yu HY,et al.Simultaneous determination of nine antidepressants in human plasma by UPLC-MS/MS [J].Chin J Clin Pharmacol(中国临床药理学杂志),2016,32(23):2191-2194.
[2] Hiemke C,Baumann P,Bergemann N,et al.AGNP consensus guidelines for therapeutic drug monitoring in psychiatry:Update 2011 [J].Practical Pharma Clin Remedies(实用药物与临床),2016,19(10):1193-1218.
[3] Taubel J,Ferber G,Fox G,et al.Thorough QT study of the effect of intravenous amisulpride on QTc interval in caucasian and japanese healthy subjects [J].Br J Clin Pharmacol,2017,83(2):339-348.
[4] Sparshatt A,Taylor D,Patel MX,et al.Amisulpride - dose,plasma concentration,occupancy and response:Implications for therapeutic drug monitoring [J].Acta Psychiatr Scand,2009,120(6):416-428.
[5] Liu FZ,Hu ZF,Wang JH.A study on the relationship between clinical efficacy of sulpiride and serum concentration [J].Shandong Arch Psychiatry(山东精神医学),2003,16(1):26-27.
[6] Chen ML,Song LS,Gao ZS,et al.The relationship between sulpiride plasma concentration and its adverse effect [J].Shanghai Archives of Psychiatry(上海精神医学),1998,10(3):161-162.
[7] Wille SM,Cooreman SG,Neels HM,et al.Relevant issues in the monitoring and the toxicology of antidepressants [J].Crit Rev Clin Lab Sci,2008,45(1):25-89.
[8] CSLM.The development and management suggestion of laboratory developed tests in china [J].Chin J Lab Med(中华检验医学杂志),2017,40(3):162-164.
[9] Ch.P.Vol Ⅰ(中国药典.一部)[S].2015:363.
[10] Wang ST,Li Y.Development of aUPLC-MS/MS method for routine therapeutic drug monitoring of aripiprazole,amisulpride,olanzapine,paliperidone and ziprasidone with a discussion of their therapeutic reference ranges for chinese patients [J].Biomed Chromatogr:BMC,2017,31(8).
[11] Tang Y,Yu Q,Nan F,et al.Simultaneous quantitative determination of rotundine and sulpiride in human plasma with liquid chromatography-tandem mass spectrometry [J].J Chin Mass Spectrometry Society(质谱学报),2008,29(1):13-17.
[12] Zhao LR,Zhao H,Liu H,et al.Determination of levosulpiride in human plasma and the application in pharmacokinetics by LC-MS/MS[J].J Shenyang Pharmaceutical Univ(沈阳药科大学学报),2015,32(4):304-310.
[13] Chen XY,Hao GT,Zhang YF,et al.Determination of milnacipran in human plasma by HPLC-MS/MS [J].Chin J Clin Pharmacol(中国临床药理学杂志),2016,32(7):643-645.
[14] Qiu PY,Mai JW,Liang ZX,et al.Determination of escitalopram in human plasma by HPLC-MS/MS [J].J Guangdong Pharmaceutical Univ(广东药科大学学报),2015,31(4):432-436.
[15] Li L,Li H,Xiang YC,et al.Simultaneous determination of four antidepressants in human plasma by LC-MS/MS [J].Chin J Clin Pharm(中国临床药学杂志),2016,25(6):339-344.
[16] Liu GR,Qiao S,Yu HY,et al.Simultaneous determination of nine antidepressants in human plasma by UPLC-MS/MS [J].Chin J Clin Pharmacol(中国临床药理学杂志),2016,32(23):2191-2194.