基于Westgard多规则理论的伏立康唑药物治疗监测的HPLC-MS/MS方法学室内质控的评价

Internal Quality Control Evaluation of Therapeutic Drug Monitoring of Voriconazole by LC-MS/MS Using Westgard Multi-rule Theory

关键词:  伏立康唑  治疗药物监测  室内质控  Westgard多规则理论  质控图

Key words:  voriconazole  therapeutic drug monitoring  internal quality control  Westgard multi-rule theory  quality control chart

摘要:

目的 建立伏立康唑治疗药物监测的HPLC-MS/MS质量控制方法，应用Westgard多规则理论对质控样品进行评估。方法 精密称取分析物伏立康唑对照品和内标氟康唑对照品适量，分别用甲醇溶解，与空白血浆基质混匀并按血浆处理方法进行操作，制备含内标氟康唑的低、中、高浓度质控血浆样品(80，5 000，8 000 ng·mL^-1)，采用HPLC-MS/MS测定2020年12月随行的36组血浆质控样品，并应用Excel绘制Levey-Jennings质控图和Z-分数质控图，采用Westgard多规则理论进行室内质量评估。结果 伏立康唑低、中、高浓度质控值日内、日间RSDs分别为4.9%~5.3%，6.0%~7.1%，内标和伏立康唑的提取回收率分别为110%~112%，98%~112%，符合中国药典对生物样品检测的要求。Levey-Jennings质控图、Z-分数质控图结果均提示随行36组质控血浆样品的浓度检测结果均在可控范围内。结论 伏立康唑治疗药物监测室内质量控制体系的建立可有效提高血药浓度监测结果的准确性，为临床精准的个体化给药提供服务。

Abstract:

OBJECTIVE To establish an internal quality control method for therapeutic drug monitoring of voriconazole by HPLC-MS/MS and evaluate it by Westgard multi-rule theory. METHODS Voriconazole as analyte and fluconazole as internal standard were weighed and dissolved in methanol. Then they were added into the blank plasma matrix according to the plasma treatment method to prepare quality control products with low, medium and high concentration(80, 5 000, 8 000 ng·mL^-1). HPLC-MS/MS was applied to determine the concentrations of 36 groups of different quality control products from December 2020. The control charts of Levey-Jennings quality and Z-score were generated by Excel, and Westgard multi-rules were also used for quality assessment. RESULTS The intra-day and inter-day RSDs of low, medium and high concentration of voriconazole quality control products were 4.9%-5.3%, 6.0%-7.1%, respectively. While the extraction recovery rates of internal standard and voriconazole were 110%-112%, 98%-112%, respectively. This met the requirements of Chinese Pharmacopoeia for the detection of biological samples. The results of Levey-Jennings quality control chart and Z-score quality control chart indicated that the concentration detection results of the 36 groups of quality control plasma samples were all within the controllable range. CONCLUSION The establishment of internal quality control system for therapeutic drug monitoring of voriconazole can effectively improve the accuracy of blood drug concentration monitoring, and provide more accurate clinical individualized medication.