Standardization challenges in antipsychotic drug monitoring: insights from a national survey in Chinese TDM practices.

Objectives: Therapeutic drug monitoring (TDM) is critical for optimizing antipsychotic therapy, yet inter-laboratory comparability in China remains poor. Unstandardized practices risk suboptimal dosing and adverse effects, highlighting the need for standardization. This study evaluated TDM practices for six antipsychotics (olanzapine, clozapine, risperidone, quetiapine, aripiprazole, and paliperidone), focusing on inter-laboratory variability, quality control material suitability, and measurement system differences.

Methods: Four processed serum samples (two frozen, two lyophilized) containing the six antipsychotic drugs were distributed to over 100 laboratories. The analyses utilized LC-MS/MS, chemiluminescence immunoassays, and HPLC. Sample homogeneity, stability, matrix effects, and method precision, and accuracy were assessed systematically.

Results: Significant inter-laboratory variability occurred for six antipsychotics. Only quetiapine met the external quality assessment (EQA) requirements, with inter-laboratory coefficients of variation (CVs) ranging from 12.08 to 15.23 %. Others, especially olanzapine (CVs: 43.48-45.30 %), had poor precision (CVs>15 %). The study revealed that commercial in vitro diagnostic kits generally provided more consistent results compared to laboratory-developed tests. However, even with commercial kits, some drugs, such as aripiprazole, still showed substantial deviations. Lyophilized samples surpassed frozen ones in stability and EQA suitability, which exhibited comparable matrix effects across most assay systems.

Conclusions: Urgent standardization of Chinese TDM practices is needed, including harmonized systems and traceable calibrators. While commercial kits enhance result consistency, further efforts are required to harmonize performance across manufacturers. Lyophilized materials are optimal for EQA due to their stability and ease of transport. These findings offer actionable insights to improve the quality and comparability of antipsychotic TDM in clinical practice.