LC-MS/MS 法测定中空纤维离心超滤处理后 569 例临床样本中的游离丙戊酸浓度。

Determination of Free Valproic Acid Concentration in 569 Clinical Samples by LC-MS/MS After Hollow Fiber Centrifugal Ultrafiltration Treatment.

机构信息

Department of Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang, China.

出版信息

Ther Drug Monit. 2021 Dec 1;43(6):789-796. doi: 10.1097/FTD.0000000000000903.

DOI:10.1097/FTD.0000000000000903

PMID:33990504

Abstract

OBJECTIVE

To perform therapeutic drug monitoring of total and free plasma valproic acid (VPA) concentrations in clinical samples and to analyze the related factors.

METHODS

The total VPA concentration in plasma was determined by ultrahigh-performance liquid chromatography with precolumn derivatization with α-bromoacetophenone, and the free VPA concentration was determined by liquid chromatography-tandem mass spectrometry after the plasma was treated by hollow fiber centrifugal ultrafiltration. Regression analysis was performed to examine the associations between free plasma VPA, total plasma VPA, and the plasma protein binding rate. The impact of individual situations, outpatient or inpatient factors, and drug combinations on VPA concentrations were examined.

RESULTS

Of the 569 clinical samples, 268 were inpatients and 301 were outpatients, and the total VPA concentration in 138 cases (24.2%) was lower than the effective treatment concentration range; the total and free VPA concentrations in outpatient samples were 11.0% and 26.1% higher than those of inpatients, respectively. There was no linear relationship between the free and total VPA concentrations. The relationship equation between the plasma protein binding rate and free VPA concentrations was as follows: Y = 0.0255X2 - 1.1357X + 97.429 (r = 0.8011). The total and free VPA concentrations were significantly decreased after the coadministration of phenobarbital (83.7% and 64.3% of the control group, P < 0.05) or carbapenem antibiotics (32.0% and 32.7% of the control group, P < 0.05).

CONCLUSIONS

The total VPA concentrations in patients with epilepsy at our hospital was lower than the effective treatment concentration range, which was inadequate for epilepsy control; the total VPA concentrations of outpatients were higher than those of inpatients; as phenobarbital affects VPA metabolism, therapeutic drug monitoring is recommended. Carbapenem antibiotic coadministration with VPA should be avoided because carbapenem antibiotics can lead to the failure of VPA antiepileptic treatment.

摘要

目的

对临床样本中的总游离血浆丙戊酸（VPA）浓度进行治疗药物监测，并分析相关因素。

方法

采用柱前衍生化的超高效液相色谱法测定血浆中的总 VPA 浓度，采用中空纤维离心超滤法处理血浆后，用液相色谱-串联质谱法测定游离 VPA 浓度。回归分析考察游离血浆 VPA、总血浆 VPA 与血浆蛋白结合率之间的相关性。考察个体情况、门诊或住院因素、药物组合对 VPA 浓度的影响。

结果

在 569 份临床样本中，268 份为住院患者，301 份为门诊患者，138 例（24.2%）患者的总 VPA 浓度低于有效治疗浓度范围；门诊样本的总 VPA 和游离 VPA 浓度分别比住院患者高 11.0%和 26.1%。游离 VPA 与总 VPA 浓度之间无线性关系。血浆蛋白结合率与游离 VPA 浓度的关系方程为：Y=0.0255X2-1.1357X+97.429（r=0.8011）。苯巴比妥（对照组的 83.7%和 64.3%，P<0.05）或碳青霉烯类抗生素（对照组的 32.0%和 32.7%，P<0.05）联合用药后，总 VPA 和游离 VPA 浓度均显著降低。