Westgard多规则理论在左乙拉西坦治疗药物监测室内质控评估中的应用

doi:10.5246/jcps.2026.03.016

中国药学(英文版) ›› 2026, Vol. 35 ›› Issue (3): 243-254.DOI: 10.5246/jcps.2026.03.016

Westgard多规则理论在左乙拉西坦治疗药物监测室内质控评估中的应用

李会婷¹^,^#, 吴妍¹^,^#, 付恩桃², 史天陆¹^,^*()

^1. 中国科学技术大学附属第一医院/安徽省立医院药学部, 安徽合肥 230001
^2. 合肥职业技术学院生物工程学院, 安徽合肥 238000

收稿日期:2025-09-12 修回日期:2025-10-29 接受日期:2026-01-06 出版日期:2026-04-04 发布日期:2026-04-03
通讯作者: 史天陆

Application of Westgard multi-rule theory to internal quality control evaluation of therapeutic drug monitoring of levetiracetam

Huiting Li¹^,^#, Yan Wu¹^,^#, Entao Fu², Tianlu Shi¹^,^*()

^1. Department of Pharmacy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui, China
^2. Department of Biotechnology Applications, Hefei Vocational and Technology College, Hefei 238000, Anhui, China

Received:2025-09-12 Revised:2025-10-29 Accepted:2026-01-06 Online:2026-04-04 Published:2026-04-03
Contact: Tianlu Shi
About author:
^# These authors contributed equally to this work.
Supported by:
The Support Program Special Grant of Anhui Pharmacist Association (Grant No. SPSG2023001005); the Key Program of Natural Science Research of Higher Education of Anhui Province (Grant No. 2023AH052545).

摘要/Abstract

摘要：

本研究基于Westgard多规则理论建立一种简便、有效、准确的癫痫患者血清左乙拉西坦治疗药物监测的内部质量控制体系, 以保证分析结果的准确性。建立高效液相色谱二极管阵列检测方法测定人血清中左乙拉西坦浓度, 自制低、中、高浓度(2.5、10、50 μg/mL)左乙拉西坦的血清质控品并进行测定, 收集相关的回顾性质控数据进行分析。使用Microsoft Excel生成Levey-Jennings质量控制图和Z-分数质量控制图, 采用Westgard多规则理论对左乙拉西坦质控结果进行评估。结果发现, 左乙拉西坦血清质量浓度在1~80 μg/mL浓度范围内呈线性, 相关系数≥ 0.997, 定量下限为0.5 μg/mL。低、中、高浓度质控品的日内和日间精密度RSD分别为1.03%–6.9%、1.63%–8.19%, 日内日间提取回收率分别为74.20%–83.85%和70.65%–83.72%, 准确度为96.26%–109.31%。通过Levey-Jennings质控图、Z-分数图结合Westgard多规则理论对20批质控品进行评价, 结果显示所有批次均未失控。该方法简便、快速、可靠且准确, 适用于人血清左乙拉西坦血药浓度的常规监测。左乙拉西坦治疗药物监测室内质量控制体系的建立有助于提高血药浓度监测结果的准确性, 为临床提供精准的个体化药学服务。

关键词: 左乙拉西坦, 治疗药物监测, 室内质量控制, Westgard多规则理论

Abstract:

This study aimed to develop a simple, effective, and accurate internal quality control (IQC) method for therapeutic drug monitoring (TDM) of levetiracetam (LEV) in the serum of patients with epilepsy and to evaluate its performance using the Westgard multi-rule criteria, thereby ensuring the analytical quality of the assays. A high-performance liquid chromatography method with diode array detection was established and validated for the quantitative determination of LEV in 100 μL of human plasma. Quality control (QC) samples at low, medium, and high concentrations (2.5, 10, and 50 μg/mL) were prepared in-house, and retrospective IQC data associated with routine TDM of LEV in our laboratory were collected for analysis. Levey-Jennings and Z-score charts were generated using Microsoft Excel, and the TDM assays were assessed according to Westgard multi-rules. Calibration curves demonstrated excellent linearity over a LEV concentration range of 1–80 μg/mL, with correlation coefficients ≥ 0.997 and a lower limit of quantification of 0.5 μg/mL. Intra-day and inter-day coefficients of variation for the low, medium, and high concentration QC samples ranged from 1.03% to 6.90% and 1.63% to 8.19%, respectively, while extraction recovery rates were 74.20%–83.85% and 70.65%–83.72%, respectively. The accuracy of the assay ranged from 96.26% to 109.31%. Twenty batches of QC samples were evaluated using Levey-Jennings and Z-score charts in combination with Westgard multi-rules, and none were found to be out of control. Taken together, this internally developed QC method was simple, rapid, reliable, and accurate for routine TDM of LEV. Its application enhanced the reliability and precision of LEV measurement and supported the rational and safe clinical use of this antiepileptic drug.

Key words: Levetiracetam, Therapeutic drug monitoring, Internal quality control, Westgard multi-rule theory

Supporting:

李会婷, 吴妍, 付恩桃, 史天陆. Westgard多规则理论在左乙拉西坦治疗药物监测室内质控评估中的应用[J]. 中国药学(英文版), 2026, 35(3): 243-254.

Huiting Li, Yan Wu, Entao Fu, Tianlu Shi. Application of Westgard multi-rule theory to internal quality control evaluation of therapeutic drug monitoring of levetiracetam[J]. Journal of Chinese Pharmaceutical Sciences, 2026, 35(3): 243-254.

图/表 6

Figure 1. High-performance liquid chromatograms obtained by injecting 10 μL of (A) blank plasma; (B) blank plasma spiked with LEV and IS; (C) plasma specimen of a patient treated with LEV (1000 mg/d) and IS; (D): blank plasma spiked with LEV, LTG, OXC, CBZ, VPA, and IS. LEV, levetiracetam; IS, internal standard; LTG, lamotrigine; OXC, oxcarbazepine; VPA, valproic.

Table 1. Intra-day and inter-day precision, accuracy, and absolute recovery of LEV.

Table 2. The stability of LEV in low (2.5 μg/mL) and high (50 μg/mL) concentrations.

Table 3. Target value and control line of QC products with low, medium, and high concentrations (n = 60).

Figure 2. Levey-Jennings curves of LEV QC products with high (A), medium (B), and low (C) concentrations, and the Z-score chart of LEV QC products (D).

Table 4. Plasma LEV concentrations obtained in patients with epilepsy treated with 1000 mg/d LEV.

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Westgard多规则理论在左乙拉西坦治疗药物监测室内质控评估中的应用

Application of Westgard multi-rule theory to internal quality control evaluation of therapeutic drug monitoring of levetiracetam

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