COVID-19疫情常态化防控下加热灭活处理血液标本对非典型抗精神病药治疗药物监测的影响

Effect of Heating and Inactivating Blood Specimens on Therapeutic Drug Monitoring of Atypical Antipsychotic Drugs Under the Normalized Prevention and Control of COVID-19 Epidemic

关键词:  新型冠状病毒  加热灭活  治疗药物监测  非典型抗精神病药物

Key words:  SARS-CoV-2  heat-inactivation  therapeutic drug monitoring  atypical antipsychotics

摘要:

目的 研究加热灭活处理血液样本对非典型抗精神病药治疗药物监测的影响。方法 血清样本采用56℃加热30 min进行灭活。使用蛋白沉淀法处理样本，采用高效液相色谱-串联质谱法测定样本中利培酮、帕利哌酮（9-OH利培酮）、奥氮平、喹硫平、阿立哌唑和氨磺必利的浓度，分别考察灭活后样品的基质效应、准确度和精密度。收集临床样本，采用配对t检验，比较临床样本灭活前后目标物浓度差异。结果 血清样本经灭活处理后，6个目标物低、中、高浓度水平内标归一化基质因子RSD均<15%，批内及批间准确度在±15%内，批内及批间精密度均<15%。临床样品利培酮、帕利哌酮、奥氮平、喹硫平、阿立哌唑灭活前后浓度无显著差异；氨磺必利灭活前后差异有统计学意义（P<0.05）。结论 利培酮、帕利哌酮、奥氮平、喹硫平、阿立哌唑的血液标本可用56℃加热30 min进行灭活后测定，而氨磺必利加热灭活处理后样本中浓度显著增加，该方法不适用其治疗药物监测。

Abstract:

OBJECTIVE To investigate the effect of heat-inactivation of blood samples on therapeutic drug monitoring (TDM) of atypical antipsychotics. METHODS Since plasma sample was collected, it was heated at 56℃ for 30 min, and then extracted by protein precipitation. High performance liquid chromatography tandem mass spectrometry was employed for quantification of risperidone, paliperidone(9-OH risperidone), olanzapine, quetiapine, aripiprazole and amisulpride. Matrix effects, accuracies and precisions of quality control samples after inactivation were investigated. Paired sample t-test was used to evaluate the difference of the concentration of the clinical samples before and after inactivation. RESULTS Related standard deviations(RSD) of internal standard normalized matrix factors or low, middle and high concentrations of the 6 compounds after inactivation were all less than 15%. Inter and intra batch accuracies were within ±15% and those of precisions were under 15%. No difference was found before and after inactivation for risperidone, paliperidone, olanzapine, quetiapine and aripiprazole, while which of amisulpride was significant different(P<0.05). CONCLUSION Heat-inactivation at 56℃ for 30 min can be applied in TDM samples containing risperidone, paliperidone, olanzapine, quetiapine and aripiprazole, while the concentration of amisulpride is significantly increased and therefore heat-inactivation is not appropriate for samples containing amisulpride.