Application of the Westgard Multi-rule Theory to Internal Quality Control Evaluation of Voriconazole for Therapeutic Drug Monitoring

Abstract

Background: There is no worldwide recognized reference internal quality control method for Therapeutic Drug Monitoring (TDM) of voriconazole (VCZ) by Liquid Chromatography (LC). In this study, we aimed to develop an internal quality control method for TDM of VCZ, evaluate it by the Westgard multi-rule theory, and guarantee the analytical quality of the assays. Methods: The plasma concentration of VCZ was detected by two-dimensional liquid chromatography with ultraviolet detection (2D-LC-UV) method. The internal quality control results accompanying with TDM of VCZ in our laboratory from July 2019 to January 2020 were collected and retrospectively studied. The Levey-Jennings quality chart and Z-score quality chart were drawn and Westgard multirules of 12s/13s/22s/R4s/41s/10x were applied to assess the suitable quality control method for TDM of VCZ. Results: The 2D-LC-UV method was well suited to monitor the plasma concentration of VCZ and increase the real-time capability of TDM for VCZ. Combined with Westgard multi-rules, the quality control charts of Levery-Jennings and Z-score both can timely discover and judge the systematic errors and random errors for the internal quality control results. 86 batches of quality control products were assessed and 7 times warnings and 6 times out of control were detected. Conclusion: The Westgard multi-rules, with high efficacy in determining detection errors, has important application value in the internal quality control for TDM of VCZ. The developed quality control method can improve the accuracy and reliability for VCZ measurement by the 2D-LC-UV method and further promote the clinical rational use of the drug.