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

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.