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：2023-02-22

- 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
- Published：30 December 2022，
  
  Received：31 May 2022，
  
  Revised：12 October 2022，
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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 ^Δ[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 ^Δ[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

德拉马尼血药浓度耐多药结核病高效液相色谱-串联质谱法

Keywords

plasma concentrationmultidrug resistant tuberculosisLC-MS/MS

references

ESPINOSA-PEREIRO J，SÁNCHEZ-MONTALVÁ A，AZNAR M L，et al. MDR tuberculosis treatment[J]. Medicina（Kaunas），2022，58（2）：188.

World Health Organization. Global tuberculosis report 2020[R]. Geneva：WHO，2020.

MIRZAYEV F，VINEY K，LINH N N，et al. World Health Organization recommendations on the treatment of drug-resistant tuberculosis，2020 update[J]. Eur Respir J，2021，57（6）：2003300.

PECORA F，DAL CANTO G，VERONESE P，et al. Treatment of multidrug-resistant and extensively drug-resistant tuberculosis in children：the role of bedaquiline and delamanid[J]. Microorganisms，2021，9（5）：1074.

MUDDE S E，UPTON A M，LENAERTS A，et al. Delamanid or pretomanid? A solomonic judgement![J]. J Antimicrob Chemother，2022，77（4）：880-902.

KUHLIN J，STURKENBOOM M G G，GHIMIRE S，et al. Mass spectrometry for therapeutic drug monitoring of anti-tuberculosis drugs[J]. Clin Mass Spectrom，2019，14（Pt A）：34-45.

RECKERS A，HUO S，ESMAIL A，et al. Development and validation of a liquid chromatography-tandem mass spectrometry method for quantifying delamanid and its metabolite in small hair samples[J]. J Chromatogr B Analyt Technol Biomed Life Sci，2021，1169：122467.

HU M H，ZHENG C L，GAO F. Use of bedaquiline and delamanid in diabetes patients：clinical and pharmacological considerations[J]. Drug Des Devel Ther，2016，10：3983-3994.

国家药典委员会.中华人民共和国药典：四部[S]. 2020年版.北京：中国医药科技出版社，2020：466-472.

LI Y，SUN F，ZHANG W H. Bedaquiline and delamanid in the treatment of multidrug-resistant tuberculosis：pro-mising but challenging[J]. Drug Dev Res，2019，80（1）：98-105.

HE W C，LIU C F，LIU D X，et al. Prevalence of Mycobacterium tuberculosis resistant to bedaquiline and delamanid in China[J]. J Glob Antimicrob Resist，2021，26：241-248.

GHOSH S，BREITSCHEIDEL L，LAZAREVIC N，et al. Compassionate use of delamanid in adults and children for drug-resistant tuberculosis：5-year update[J]. Eur Respir J，2021，57（5）：2002483.

NGUYEN T V A，ANTHONY R M，CAO T T H，et al. Delamanid resistance：update and clinical management[J]. Clin Infect Dis，2020，71（12）：3252-3259.

陆宇，朱慧. 抗结核药治疗药物监测临床应用专家共识[J]. 中国防痨杂志，2021，43（9）：867-873.

刘胜兰，唐智，陈磊，等. UPLC-MS/MS法测定人血浆中20（S）-原人参二醇的浓度[J]. 中国药房，2021，32（18）：2248-2253.

朱慧，刘忠泉，谢莉，等. 贝达喹啉的HPLC-MS/MS检测方法建立及应用[C]//耐药结核病临床诊治难点与热点问题专题研讨会资料汇编. [出版者不详]. 2018：138-142.

林强，杨超，李美丽，等. 超高效液相色谱-串联质谱法同时测定血浆与尿液中12种脂溶性贝类毒素[J]. 色谱，2021，39（4）：399-405.

MENG M，SMITH B，JOHNSTON B，et al. Simultaneous quantitation of delamanid（OPC-67683）and its eight metabolites in human plasma using UHPLC-MS/MS[J]. J Chromatogr B Analyt Technol Biomed Life Sci，2015，1002：78-91.

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