UPLC-MS/MS法对比不同血药浓度下氯氮平、氯丙嗪与利培酮对精神分裂症患者 肾功能的影响

Comparison of the Effects of Clozapine, Chlorpromazine, and Risperidone on Renal Function in Schizophrenia Patients at Different Plasma Drug Concentrations Using UPLC-MS/MS Method

摘要: 目的：探讨氯氮平、氯丙嗪及利培酮三种常用抗精神病药物在不同血药浓度下对精神分裂症患者肾功能的影响，明确兼具疗效与肾脏安全性的血药浓度区间，为临床个体化用药提供科学依据。方法：采用前瞻性病例对照研究设计，选取2024年11月至2025年11月十堰市中医医院住院的18~65岁精神分裂症患者180例，按用药类型分为氯氮平组、氯丙嗪组、利培酮组，每组60例，再根据血药浓度分为低、中、高浓度亚组(各20例)。采用超高效液相色谱–串联质谱(UPLC-MS/MS)法测定患者血药浓度，全自动生化分析仪检测肾功能指标(血清肌酐、尿素氮)。运用SPSS23.0 软件进行统计学分析，计量资料以均数 ± 标准差($\overline{x}\pm s$ )表示，组间比较采用t检验，计数资料采用χ²检验，以P < 0.05为差异有统计学意义。结果：氯氮平组和氯丙嗪组高浓度亚组的血清肌酐、尿素氮水平显著高于中、低浓度亚组(P < 0.05)；利培酮组各浓度亚组肾功能指标差异无统计学意义(P > 0.05)。相同血药浓度区间下，氯丙嗪组肾功能指标升高幅度最大，氯氮平组次之，利培酮组最小。结论：氯氮平与氯丙嗪对精神分裂症患者肾功能的影响具有血药浓度依赖性，高浓度时肾脏损害风险增加；利培酮对肾功能影响较小且无明显浓度依赖性。临床需结合UPLC-MS/MS监测的血药浓度调整给药方案，氯氮平与氯丙嗪宜控制在中低浓度区间，以平衡疗效与肾脏安全性。

Abstract: Objective: To investigate the effects of three commonly used antipsychotic drugs, clozapine, chlorpromazine, and risperidone, on renal function in patients with schizophrenia at different plasma drug concentrations, and to identify the plasma concentration range that combines efficacy and renal safety, providing a scientific basis for individualized clinical medication. Methods: A prospective case-control study design was adopted. A total of 180 patients aged 18 to 65 years with schizophrenia admitted to Shiyan Traditional Chinese Medicine Hospital from November 2024 to November 2025 were selected and divided into clozapine, chlorpromazine, and risperidone groups, with 60 patients in each group. These groups were further divided into low, medium, and high concentration subgroups (20 patients in each subgroup) based on plasma drug concentrations. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to measure plasma drug concentrations in patients, and an automatic biochemical analyzer was used to detect renal function indicators (serum creatinine and blood urea nitrogen). Statistical analysis was performed using SPSS 23.0 software. Measurement data were expressed as mean ± standard deviation ($\overline{x}\pm s$ ), and t-tests were used for inter-group comparisons. Count data were analyzed using χ² tests, with P < 0.05 indicating statistical significance. Results: The serum creatinine and blood urea nitrogen levels in the high concentration subgroups of the clozapine and chlorpromazine groups were significantly higher than those in the medium and low concentration subgroups (P < 0.05); there were no significant differences in renal function indicators among the risperidone subgroups at different concentrations (P > 0.05). Within the same plasma drug concentration range, the increase in renal function indicators was greatest in the chlorpromazine group, followed by the clozapine group, and the smallest in the risperidone group. Conclusion: The effects of clozapine and chlorpromazine on renal function in patients with schizophrenia are plasma drug concentration-dependent, with an increased risk of renal damage at high concentrations; risperidone has a smaller impact on renal function and no significant concentration dependence. Clinically, it is necessary to adjust the medication regimen based on plasma drug concentrations monitored by UPLC-MS/MS. Clozapine and chlorpromazine should be controlled within the medium and low concentration ranges to balance efficacy and renal safety.