Abstract��OBJECTIVE To develop and validate an HPLC-MS/MS method for the measurement of 11 antipsychotics in human plasma samples for TDM(therapeutic drug monitoring) or other objectives. METHODS Protein precipitation method with acetonitrile was used to extract the drugs in plasma. Agilent Poroshell 120 EC-C18 column(2.1 mm��50 mm, 2.7 ��m)was used for chromatographic separation. The mobile phase was acetonitrile with 0.1% formic acid-water with 0.1% formic acid gradiently eluted at a flow rate of 0.3 mLmin-1. The injection volume was 5 ��L. The deprotonated ions of analytes were ionized by electrospray(ESI) and detected in positive ionization by multiple reaction monitoring mode(MRM). RESULTS The total run time of the chromatographic separation and mass detection was 6 min. Excellent linear relationship with correlation coefficient of 0.99 was obtained from 2 to 200 ngmL-1 for risperidone, paliperidone and olanzapine, from 10 to 1 000 ngmL-1 for aripiprazole, quetiapine, amisulpride, clozapine, chlorpromazine and sulpride, from 0.4 to 40 ngmL-1 for haloperidol, and 0.2 to 20 ngmL-1for perphenazine, respectively. The precision and accuracy varied from 2.7% to 10.8% and from 90.7% to 102.7%, respectively. CONCLUSION This established method is simple, rapid, and economic, fulfilling all criteria for TDM, and could be successfully applied in the routine TDM of antipsychotics in clinic.
������,�±��,������. ͬʱ�����Ѫ����11�����ƾ���ҩ��Ũ�ȵ�HPLC-MS/MS�����Ľ���[J]. �й�ҩѧ��־, 2018, 53(10): 808-816.
XU Xiang-zhen, CHEN Bin-bin, LV Hai-yan. Development and Validation of HPLC-MS/MS Method for Simultaneous Quantitation of Eleven Antipsychotics in Human Plasma. Chinese Pharmaceutical Journal, 2018, 53(10): 808-816.
GRUNDMANN M, KACIROVA I, URINOVSKA R.Therapeutic drug monitoring of atypical antipsychotic drugs. Acta Pharm, 2014, 64(4):387-401.
[2]
HIEMKE C, BAUMANN N, CONCA A, et al. AGNP Consensus guidelines for therapeutic drug monitoring in psychiatry: update 2011. Pharmacopsychiatry, 2011, 44(6):195-235.
[3]
SISTIK P, TURJAP M, IORDACHE A M, et al. Quantification of selected antidepressants and antipsychotics in clinical samples using chromatographic methods combined with mass spectrometry: a review(2006-2015). Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub, 2016, 160(1):39-53.
[4]
DE MEULDER M, WALDRON M, LI L, et al. Development and validation of HILIC-ESI/MS/MS methods for simultaneous quantitation of several antipsychotics in human plasma and blood. Bioanalysis, 2016, 8(8):765-794.
[5]
ZHANG M Q, JIA J Y, LU X P, et al. Simultaneous determination of five antipsychotics and nine antidepressants in human serum by LC-MS/MS. Chin Pharm J(�й�ҩѧ��־), 2011, 46(1):57-60.
[6]
ZHONG D F, LI G, LIU C X.Principle guidelines for quantitative analysis of biological samples-draft. J Drug Eval Res(ҩ�������о�), 2011, 34(6):409-415.
[7]
US Department of Health and Human Services. Guidance for Industry:Bioanalytical Method Validation. Food and Drug Administration.2001. Available at: http://www.fda.gov/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/default.htm.
[8]
LOPEZMD, LEONARDO V, JOHN M, et al. Recommendations for the monitoring of serum concentrations of antipsychotic drugs in the treatment of schizophrenia. J Clin Psychiatry, 2015, 76(9):1249-1250.
[9]
OLESEN O V, LINNET K. Determination of olanzapine in serum by high-performance liquid chromatography using ultraviolet detection considering the easy oxidability of the compound and the presence of other psychotropic drugs. J Chromatogr B Biomed Sci Appl, 1998, 714(2):309-315.
[10]
WANG J, HUANG H, YAO Q, et al. Simple and accurate quantitative analysis of 16 antipsychotics and antidepressants in human plasma by ultrafast high-performance liquid chromatography/tandem mass spectrometry. Ther Drug Monit, 2015, 37(5):649-660.
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