利培酮血药浓度与甲状腺功能的相关性研究

Study on the correlation between blood concentration of risperidone and thyroid function indexes

刘恺 ¹梁俊 ¹聂丽娟 ¹曹银 ¹戴彪 ¹杨陈晨 ¹夏清荣¹

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作者信息

1. 安徽医科大学附属心理医院,安徽合肥230022;安徽省合肥市第四人民医院药剂科,230022;安徽省精神卫生中心精神药理研究室,安徽合肥230022;安徽省精神心理疾病临床医学研究中心,安徽合肥230022
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摘要

目的:建立利培酮(RIS)血药浓度测定方法,探讨RIS治疗精神分裂症病人的血药浓度与甲状腺功能指标的相关性.方法:血浆样品经乙腈沉淀后,以氯米帕明为内标,采用超高效液相色谱-串联质谱(UPLC-MS/MS)法测定,色谱柱为BEH C18,流动相为乙腈-水(含5 mmol/L乙酸铵溶液和0.01％氨水),梯度洗脱,流速为0.5 mL/min,柱温为40℃,进样量为2μL,采用多反应监测模式扫描,对UPLC-MS/MS进行方法学考察,将其用于测定116例临床精神分裂症病人血浆中RIS浓度,收集相关病例的住院信息,并探讨RIS血药浓度与甲状腺功能指标的相关性.结果:RIS、9-羟基利培酮(9-OHRIS)在0.4～120.0 ng/mL范围内线性关系良好;日内、日间准确度、提取回收率、基质效应及稳定性均符合要求.病人体内平均稳态血药质量浓度为(49.76±18.07)ng/mL;治疗各时间点病人的稳态血药浓度差异无统计学意义(P>0.05),甲状腺功能指标除促甲状腺激素外(P>0.05),其他4个指标治疗后随着时间的推移呈波动上升趋势(P<0.01);病人的血药浓度与甲状腺功能指标无相关性(P>0.05),但女性病人的RIS血药浓度与四碘甲状腺原氨酸、游离三碘甲状腺素、游离甲状腺素均呈正相关(r=0.480、0.524、0.454,P<0.05).结论:该方法准确简便、快速灵敏、重现性好,可用于测定精神分裂症病人体内RIS的血药浓度.女性病人体内较高的血药浓度可能会影响甲状腺功能指标,进而影响病人甲状腺功能,需要引起临床的注意.

Abstract

Objective:To establish a method for the determination of blood concentration of risperidone (RIS),and to explore the correlation between blood concentration of RIS and thyroid function indexes in patients with schizophrenia. Methods:The plasma samples were precipitated with acetonitrile,and then determined by ultra performance liquid chromatography-tandem mass spectrometry ( UPLC-MS/MS) with clomipramine as the internal standard. The chromatographic column was BEH C18 , and the mobile phase was acetonitrile-water (containing 5 mmol/L ammonium acetate solution and 0. 01％ ammonia ) with gradient elution. The flow rate was 0. 5 mL/min,the column temperature was 40 ℃, and the injection volume was 2 μL. The methodology of UPLC-MS/MS was investigated by multiple reaction monitoring scanning,and it was used to determine the plasma RIS concentration in 116 patients with schizophrenia. The hospitalization information of related cases was collected,and the correlation between RIS blood concentration and thyroid function indexes was explored. Results:RIS and 9-OHRIS had a good linear relationship in the concentration range of 0. 4 -120. 0 ng/mL. The intra-day and inter-day accuracy,extraction recovery,matrix effect and stability met the requirements. The mean steady-state plasma concentration was ( 49. 76 ± 18. 07 ) ng/mL. There was no significant difference in the steady-state plasma concentration of patients at each time point of treatment (P>0. 05). Except for TSH (P>0. 05),the other four indicators showed a fluctuating upward trend over time after treatment (P <0. 05),but the RIS plasma concentration of female patients was positively correlated with T4,FT3 and FT4 (r=0. 480,0. 524,0. 454,P<0. 05). Conclusions:The method is accurate,simple,rapid,sensitive and reproducible,and can be used to determine the plasma concentration of RIS in patients with schizophrenia. Higher blood drug concentration in female patients may affect the thyroid function index, and then affect the thyroid function of patients, which needs clinical attention.

关键词

精神分裂症/利培酮/血药浓度/甲状腺功能

Key words

schizophrenia/risperidone/plasma concentration/thyroid function

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基金项目

合肥市第七周期重点专科资助项目(合卫医秘[2023]72号)

安徽省临床卫生重点专科资助项目(卫医秘[2022]105号)

出版年

2024

蚌埠医学院学报

蚌埠医学院

蚌埠医学院学报

CSTPCD

影响因子：0.917

ISSN：1000-2200

参考文献量17

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