Establishment and application of a method for the determination of plasma concentration of delamanid

DING Qiaoyan; ZHANG Huan; MA Lihua; LI Sisi; ZHANG Yu; ZHOU Ming

doi:10.6039/j.issn.1001-0408.2022.24.17

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Establishment and application of a method for the determination of plasma concentration of delamanid

更新时间：2025-09-26

- Establishment and application of a method for the determination of plasma concentration of delamanid
- ZHONGGUO YAOFANG Vol. 33, Issue 24, Pages: 3029-3033(2022)
- 作者机构：
  
  武汉市肺科医院药学部，武汉　430030
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2022.24.17
  CLC： R917
- Received：31 May 2022，
  
  Revised：2022-10-12，
  
  Published：30 December 2022
- 稿件说明：
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丁巧燕,张欢,马丽华,等.德拉马尼血药浓度测定方法的建立及应用[J].中国药房,2022,33(24):3029-3033.

DING Qiaoyan,ZHANG Huan,MA Lihua,et al.Establishment and application of a method for the determination of plasma concentration of delamanid[J].ZHONGGUO YAOFANG,2022,33(24):3029-3033.
丁巧燕,张欢,马丽华,等.德拉马尼血药浓度测定方法的建立及应用[J].中国药房,2022,33(24):3029-3033. DOI： 10.6039/j.issn.1001-0408.2022.24.17.

DING Qiaoyan,ZHANG Huan,MA Lihua,et al.Establishment and application of a method for the determination of plasma concentration of delamanid[J].ZHONGGUO YAOFANG,2022,33(24):3029-3033. DOI： 10.6039/j.issn.1001-0408.2022.24.17.

摘要

目的

建立测定德拉马尼（DLM）血药浓度的方法并应用。

方法

血浆样品经甲醇沉淀蛋白后，采用超高效液相色谱-串联质谱（LC-MS/MS）法检测。色谱柱为Phenomenex Synergi

Fusion-RP，流动相为甲醇-0.1%甲酸溶液（梯度洗脱），柱温为40 ℃，流速为0.3 mL/min，进样量为1 μL；离子源为电喷雾离子源，以多反应监测模式进行正离子扫描，用于定量分析的DLM离子对为

m/z

535.0→352.0。采用上述LC-MS/MS法测定6例耐多药结核病（MDR-TB）患者体内DLM的血药浓度。

结果

DLM检测质量浓度的线性范围为0.05～8 μg/mL（

＝0.999 5），定量下限为0.05 μg/mL；日内、日间精密度RSD均小于10%，准确度为92.7%～104.9%，平均基质效应为94.3%～107.5%，平均萃取回收率为93.2%～98.1%。6例MDR-TB患者体内DLM的血药浓度为0.61～2.76 μg/mL，平均（1.67±0.74）μg/mL。

结论

所建LC-MS/MS法专属性好，灵敏度、准确度及精密度均高，可用于MDR-TB患者体内DLM血药浓度的检测。

Abstract

OBJECTIVE

To establish and apply a method for the determination of plasma concentration of delamanid （DLM）.

METHODS

After plasma samples were treated with methanol precipitation， LC-MS/MS was adopted to determine the plasma concentration of DLM. The chromatographic column was Phenomenex Synergi

Fusion-RP with mobile phase of methanol-0.1% formic acid solution （gradient elution）. The column temperature was 40 ℃， the flow rate was 0.3 mL/min， and the sample size was 1 μL. The ion source was electrospray ion source， and positive ion scanning was carried out in multi-reaction monitoring mode. The DLM ion pair used for quantitative analysis was

535.0→352.0. The plasma concentration of DLM in 6 multidrug resistant tuberculosis （MDR-TB） patients were determined by the LC-MS/MS method.

RESULTS

The linear range of DLM was 0.05-8 μg/mL （

＝0.999 5）， and the lowest limit of quantitation was 0.05 μg/mL. RSDs of intra-batch and inter-batch precision were all less than 10%. The accuracy ranged 92.7%-104.9%. Average matrix effect was 94.3%-107.5%. Average recoveries were 93.2%-98.1%. The plasma concentration of DLM in 6 MDR-TB patients ranged from 0.61-2.76 μg/mL， with an average of （1.67±0.74） μg/mL.

CONCLUSIONS

The established LC-MS/MS analysis method has good specificity， high sensitivity， accuracy and precision， and can be used to determine DLM plasma concentration in MDR-TB patients.

关键词

Keywords

references

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