中国药物警戒 ›› 2024, Vol. 21 ›› Issue (9): 991-997.
DOI: 10.19803/j.1672-8629.20240148

• 基础与临床研究 • 上一篇    下一篇

UPLC-MS/MS法测定人血清中曲唑酮浓度及其临床个体化用药

曹银, 周旋, 戴彪, 邓逸芸, 闫春宇, 单锋, 夏清荣, 梁俊*   

  1. 安徽医科大学附属心理医院,合肥市第四人民医院药剂科,安徽省精神卫生中心精神药理研究室,安徽 合肥 230022
  • 收稿日期:2024-03-08 出版日期:2024-09-15 发布日期:2024-09-14
  • 通讯作者: *梁俊,女,硕士,副主任药师,临床药学。Email: 1309071273@qq.com
  • 作者简介:曹银,男,硕士,副主任药师,药物代谢动力学。
  • 基金资助:
    国家自然科学基金资助项目（82304847）; 合肥市第七周期重点专科资助项目; 安徽医科大学校科研基金项目（2021xkj113）; 合肥市第四人民医院院内科研项目（HFSY202109）

A UPLC-MS/MS method for determination of human serum trazodone concentration and its clinical individualized medications

CAO Yin, ZHOU Xuan, DAI Biao, DENG Yiyun, YAN Chunyu, SHAN Feng, XIA Qingrong, LIANG Jun*   

  1. Department of Pharmacy, Affiliated Psychological Hospital of Anhui Medical University, Hefei Fourth People's Hospital, Psychopharmacology Research Laboratory, Anhui Mental Health Center, Hefei Anhui 230022, China
  • Received:2024-03-08 Online:2024-09-15 Published:2024-09-14

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摘要： 目的 建立超高效液相串联质谱法（UPLC-MS/MS）测定患者血清中曲唑酮浓度,并用于曲唑酮的临床个体化用药。方法 色谱柱为MSCB-2A（2.1 mm×50 mm,2.5μm）;流动相为甲醇（B）-水（A,含0.01%氨水）,梯度洗脱（梯度设置为0~0.2 min,55% B;0.2~2.0 min,55%~95% B;2.0~2.5 min,95%~95% B;2.5~2.6 min,95%~55% B;2.6~3.0 min,55%~55% B）,流速0.5 mL·min-1,柱温40℃,进样量0.1 µL;离子源：电喷雾离子源;电离模式：正离子模式。血清经乙腈沉淀蛋白,地西泮为内标,对本方法的专属性、标准曲线和定量下限、精密度与回收率、基质效应和稳定性进行相应的考察。同时将该方法应用于16例使用曲唑酮患者的血药浓度测定,并对检测结果进行分析,给出相应的干预意见。结果 血清中曲唑酮在10.0~1 500.0 ng·mL-1内线性关系良好（R2=0.999 4）; 低、中、高3组不同质控浓度（50.0、400.0、1 000.0 ng·mL-1）日内和日间精密度的相对标准偏差（RSD）均小于7%,准确度为91.90%~98.67%;低、中、高浓度的曲唑酮血清在常温下4 h、2~8℃冰箱冷藏24 h、长期冷冻3个月以及反复冻融循环条件下稳定性良好,在各条件下准确度为95.04%~105.78%。该法已成功应用于曲唑酮临床样本治疗药物监测。结论 UPLC-MS/MS法检测曲唑酮血药浓度具有快速简便、稳定准确、灵敏度高、污染小等优点,该法可应用于曲唑酮临床个体化用药。

关键词: 曲唑酮, UPLC-MS/MS, 治疗药物监测, 血药浓度, 人血清, 个体化用药

Abstract: Objective To establish an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of trazodone concentrations in serum of patients that can be used for clinical individualized medications with trazodone. Methods The chromatographic column was MSCB-2A (2.1 mm × 50 mm, 2.5μm). The mobile phase consisted of methanol (B) -water (A, containing 0.01 % ammonia) under gradient elution (the gradient set at 0~0.2 min, 55 % B; 0.2~2.0 min, 55 %~95 % B; 2.0~-2.5 min, 95 %~95 % B; 2.5~2.6 min, 95 %~55 % B; 2. 6~3. 0 min, 55 %~55 % B). The flow rate was 0.5 mL·min- 1, the column temperature 40℃, and the injection volume 0.1 μL in a positive ion mode. The serum was precipitated by acetonitrile, and diazepam was used as the internal standard. The specificity, standard curve and lower limit of quantification, precision and recovery, matrix effect, and stability of the method were investigated. Meanwhile, this method was applied to the determination of blood concentrations of 16 patients using trazodone, and the test results were analyzed before intervention opinions were given. Results The linear range of trazodone in serum was 10.0 to 1 500.0 ng·mL-1 (R2 = 0.9994). The relative standard deviation (RSD) of intra-day and inter-day precision of low, medium, and high quality control concentration samples (50.0, 400.0, 1 000.0 ng·mL-1) was less than 7%, and the accuracy ranged from 91.90% to 98.67%. The serum with low, medium, and high concentrations of trazodone remained stable at room temperature for 4 h, for 24 h in a 2 to 8℃ refrigerator, after long-term freezing of 3 months or repeated freeze-thaw cycles. The accuracy ranged from 95.04% to 105.78% under varied conditions. The method was also applied to the therapeutic drug monitoring of clinical samples of trazodone. Conclusion This UPLC-MS/MS method is rapid, simple, stable, accurate, highly sensitive, and almost pollution-free in the detection of plasma concentrations of trazodone This method has been successfully applied to the clinical individualized medication of trazodone.

Key words: trazodone, UPLC-MS/MS, therapeutic drug monitoring, blood drug concentration, human serum, individualized medication

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