基于Westgard多规则理论建立甲氨蝶呤治疗药物监测的室内质控评估方法

Establishment of Internal Quality Control Evaluation Method of Therapeutic Drug Monitoring of Methotrexate Based on Westgard Multi-rule Theory

关键词:  甲氨蝶呤  高效液相色谱-串联质谱法  室内质控  质控图  Westgard多规则理论

Key words:  methotrexate  LC-MS/MS  internal quality control  quality control chart  Westgard multi-rule theory

摘要:

目的 建立甲氨蝶呤(methotrexate，MTX)血药浓度检测方法，并应用Westgard多规则理论对MTX血药浓度监测的室内质量控制进行评价。方法 利用LC-MS/MS建立MTX血药浓度检测方法并进行方法学验证。对实际治疗药物监测过程中低、中、高3个浓度的MTX质控样品的检测结果进行统计分析，绘制Levery-Jennings和Z分数质控图，运用Westgard多规则法对质控图进行评价。结果 MTX的定量下限为10.4 ng·mL^–1，线性范围为10.4~5 200 ng·mL^–1，各浓度日内、日间准确度及精密度均<15%，提取回收率为102.43%~103.26%，基质效应为113.58%~118.33%，符合生物样本定量分析的要求。对Levery-Jennings和Z分数质控图进行Westgard多规则质控评价发现，2020年11月期间MTX的血药浓度监测提出警告2次(违反1_2s规则)，其余样品均在控。结论 建立的MTX血药浓度检测方法专属性好，灵敏度高，快速准确，且该方法在MTX血药浓度的长期检测中具有较好的稳定性。应用质控图及Westgard多规则质控评价方法对保证MTX血药浓度检测的可靠性具有重要意义。

Abstract:

OBJECTIVE To establish a method for the content determination of methotrexate (MTX) in human plasma and to evaluate the internal quality control of MTX plasma concentration monitoring using Westgard multi-rule theory. METHODS LC-MS/MS was used to establish and validate the methodology for the determination of MTX plasma concentration.The results of MTX quality control samples with low,medium and high concentrations in the actual process of therapeutic drug monitoring were statistically analyzed.Levery-Jennings and Z-score quality control charts were drawn,and Westgard multi-rule method was used to evaluate the quality control charts.RESULTS The established method met the requirements of quantitative analysis of biological samples with a lower limit of quantitation of 10.4 ng·mL^-1,the linearity range was 10.4-5 200 ng·mL^-1,the intra-day and inter-day accuracies and precisions were all<15%,the extraction recovery ranged from 102.43% to 103.26%,and the matrix effect ranged from 113.58% to 118.33%.Using Westgard multi-rule quality control evaluation on the Levery-Jennings and Z-score quality control charts found that MTX plasma concentration monitoring during November 2020 had two warnings (violation of 1_2S rule),and the rest samples were all under control.CONCLUSION The established MTX plasma concentration detection method is specific,sensitive,rapid,accurate,and has good stability in the long-term detection of MTX plasma concentration.The application of quality control charts and Westgard multi-rule quality control evaluation is of great significance to ensure the reliability of MTX plasma concentration detection.