基于Westgard多规则理论拉莫三嗪治疗药物监测的室内质控评估

Internal Quality Control Evaluation of Therapeutic Drug Monitoring of Lamotrigine by Westgard Multi-rule Theory

关键词:  拉莫三嗪  高效液相色谱法  质控图  Westgard多规则理论  室内质控

Key words:  lamotrigine  HPLC  quality control chart  Westgard multi-rule theory  internal quality control

摘要:

目的 建立拉莫三嗪（lamotrigine，LTG）治疗药物监测的室内质量控制方法，并应用Westgard多规则理论进行评估。方法 自制高、中、低浓度（10，5，1 μg·mL^-1）LTG血浆质控品，采用HPLC-UV测定2018年10—12月随行的30组自制质控品浓度，应用Excel软件绘制Levey-Jennings质控图和Z-分数质控图，使用Westgard多规则理论进行室内质量控制评估。结果 LTG高、中、低浓度质控值日内、日间RSD分别为2.33%~9.62%，5.63%~9.07%，提取回收率分别为70.48%~78.92%，74.68%~80.77%，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30组自制质控品的浓度检测结果违反了Westgard多规则理论，提出警告1次（违反1_2s规则）、失控1次（违反2_2s规则）。经分析后发现，与LTG工作液存储时间过长有关，经重新配制后自制新批次质控品，监测数据恢复正常。结论 LTG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，提供临床更精准的个体化药学服务。

Abstract:

OBJECTIVE To establish an internal quality control method for therapeutic drug monitoring of lamotrigine (LTG) and evaluate it by Westgard multi-rule theory. METHODS Self-made LTG quality control products with high, medium and low concentration(10, 5, 1 μg·mL^-1) were prepared. HPLC-UV was applied to determine the concentrations of 30 groups of self-made different quality control products from October to December 2018 under specified experimental conditions. 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 LTG quality control products were 2.33%-9.62%, 5.63%-9.07%, respectively, while the extraction recovery rates were 70.48%-78.92%, 74.68%-80.77%, respectively. This meets the requirements of Chinese Pharmacopoeia for the detection of biological samples. Quality control charts of Levey-Jennings and Z-score showed that the results of 30 groups of self-made quality control products' concentration had violated Westgard multi-rule theory with one warning(violation of 1_2s rule) and one out of control(violation of 2_2s rule). After analysis, it was related to the long storage time of LTG working liquid and the monitoring data were returned to normal after reformulation. CONCLUSION The establishment of internal quality control system for therapeutic drug monitoring of LTG can effectively improve the accuracy of blood drug concentration monitoring, and provide more accurate clinical personalized pharmaceutical services.