瓶内处理技术结合快速LC-MS提高利培酮血药浓度测定效率

Bottle-in technology combined with rapid LC-MS to improve the determination efficiency of risperidone plasma concentration

目的 评估“瓶内处理”(Bottle-in)技术结合快速LC-MS的方法学特性,并验证其对治疗药物监测技术自动化和标准化的促进作用。方法 选择利培酮及其主要代谢物9-羟利培酮作为研究对象,针对两种血样前处理技术——Bottle-in技术与实验室现行的常规处理(RP)技术,建立并验证相应的LC-MS检测方法。实验设计遵循CLSI EP9-A3指南,对60例服用利培酮的患者血液样本应用两种方法进行利培酮和9-羟利培酮浓度的测定,并记录样本的报告时间。采用Spearman相关性分析、Passing-Bablok回归分析、Bland-Altman一致性检验以及医学决定水平(MDL)预期偏倚分析,对两种方法的检测结果进行相关性和差异性评价。结果 两种前处理技术下的LC-MS方法在测定利培酮和9-羟利培酮血药浓度时,均满足方法学验证的标准。在60例患者的样本中,两组结果均未出现异常值,显示出强烈的相关性(P<0.01)。Passing-Bablok回归模型显示了良好的线性关系。Bland-Altman一致性检验结果表明,两者具有高度一致性。MDL预期偏倚分析进一步证实,两种检测方法的结果未出现显著性偏倚,预期偏倚值(Bc)均在可接受的偏倚限值范围内。Bottle-in技术较RP技术在前处理时间上可节约66.67%,结合快速LC-MS技术对12例患者样本进行检测,全流程检出时间上Bottle-in组较RP组能缩短12.50%的时长。结论 Bottle-in技术凭借其高效的前处理方式,提高了药物监测技术自动化和标准化,可作为替代RP技术的一种有效方法,成为现代临床药学监测中的一项重要进展。

Objective To evaluate the methodological characteristics of Bottle-in technology combined with rapid liquid chromatography-mass spectrometry(LC-MS)and to validate its contribution to the automation and standardization of therapeutic drug monitoring.Methods Risperidone and its main metabolite,9-hydroxyrisperidone,were selected as the research subjects.Corresponding LC-MS detection methods were established and validated for two blood sample pretreatment techniques(Bottle-in technology and the routine processing(RP)technology currently in use in the laboratory).The experimental design followed CLSI EP9-A3 guidelines.Both methods were used to determine the concentrations of risperidone and 9-hydroxyrisperidone in the blood samples of 60 patients taking risperidone,and the report time of the samples was recorded.Spearman correlation analysis,Passing-Bablok regression analysis,Bland-Altman agreement test,and medical decision level(MDL)expected bias analysis were used to evaluate the correlation and differences between the detection results of both methods.Results The LC-MS methods with both pretreatment techniques met the methodological validation standards for the determination of risperidone and 9-hydroxyrisperidone blood drug concentrations.Results in both groups of showed no outliers in the samples of 60 patients,indicating a strong correlation(P<0.01).The Passing-Bablok regression model showed a good linear relationship.The Bland-Altman agreement test indicated a high degree of consistency between the two methods.MDL expected bias analysis further confirmed that the results of the two detection methods showed no significant bias,with the expected bias values(Bc)all within the acceptable limits.Bottle-in technology and RP technology might save 66.67%of pre-processing time.Combined with rapid LC-MS technology,the detection time of 12 patient samples in the Bottle-in group was shortened by 12.50%compared to the RP group in the entire process.Conclusion The Bottle-in technology,with its efficient sample pretreatment approach can improve the automation and standardization of therapeutic drug monitoring,which serves as an effective alternative to the RP technique,marking a significant advancement in modern clinical pharmacological monitoring.