Scholarlink

<p>Cycloserine is widely used for treatment of multidrug-resistant tuberculosis (MDR-TB) as a component of multidrug treatment regimens. There are limited reports on the pharmacokinetics of cycloserine in MDR-TB patients, especially from a high TB burden country like India. Despite longstanding clinical use, cycloserine has a narrow therapeutic index and its neuropsychiatric side effects warrant therapeutic drug monitoring to ensure safe and effective dosing. We aimed to develop a high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS)-based method for analysis of cycloserine in human plasma collected from MDR-TB patients and describe its pharmacokinetics in a pilot study. The method was developed on a reverse phase column using gradient mode and quantitated on the mass spectrometer using electron spray ionisation in a positive mode. The method linearity was obtained between 0.782 to 50&#xa0;mg/L and all other method validation parameters passed the acceptability criteria as per the U.S. FDA Bioanalytical method validation guidelines. For the pharmacokinetic analysis, whole blood was collected at 6 time points over 8-h following observed ingestion after achieving steady state. The median maximum concentration (Cmax), observed 2&#xa0;h after ingestion was found to be 16.0 (interquartile range, 11.7–20.8) mg/L and the area under curve until the 8-hour period was 121.17&#xa0;mg.h/L. This LC-MS/MS method provides a simple, robust method to quantify cycloserine concentrations in human plasma and has been successfully applied for pilot pharmacokinetic study which may support dose optimization.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Application of a Liquid Chromatography: Tandem Mass Spectrometry Based Method to Determine Plasma Cycloserine Concentrations in Indian MDR-TB Patients—A Pilot Study

  • 期刊论文

  • 发表日期：

    2026年2月2日

查看全文
  • Rohan V. Lokhande,
  • Prerna R. Arora,
  • Camilla Rodrigues,
  • Ganesh R. Bhagure,
  • Zarir F. Udwadia,
  • Amita Gupta,
  • Jeffrey A. Tornheim,
  • Tester F. Ashavaid,
  • Lancelot M. Pinto,
  • Jai B. Mullerpattan,
  • Ayesha Sunavala,
  • Jigneshkumar Patel,
  • Alpa J. Dherai,
  • Sarita Thakur,
  • Heeral Pandya,
  • Namrata Sawant,
  • Anton Joubert,
  • Lubbe Wiesner,
  • Neil A Martinson,
  • Ebrahim Variava,
  • Firdaus Nabeemeeah

摘要

Cycloserine is widely used for treatment of multidrug-resistant tuberculosis (MDR-TB) as a component of multidrug treatment regimens. There are limited reports on the pharmacokinetics of cycloserine in MDR-TB patients, especially from a high TB burden country like India. Despite longstanding clinical use, cycloserine has a narrow therapeutic index and its neuropsychiatric side effects warrant therapeutic drug monitoring to ensure safe and effective dosing. We aimed to develop a high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS)-based method for analysis of cycloserine in human plasma collected from MDR-TB patients and describe its pharmacokinetics in a pilot study. The method was developed on a reverse phase column using gradient mode and quantitated on the mass spectrometer using electron spray ionisation in a positive mode. The method linearity was obtained between 0.782 to 50 mg/L and all other method validation parameters passed the acceptability criteria as per the U.S. FDA Bioanalytical method validation guidelines. For the pharmacokinetic analysis, whole blood was collected at 6 time points over 8-h following observed ingestion after achieving steady state. The median maximum concentration (Cmax), observed 2 h after ingestion was found to be 16.0 (interquartile range, 11.7–20.8) mg/L and the area under curve until the 8-hour period was 121.17 mg.h/L. This LC-MS/MS method provides a simple, robust method to quantify cycloserine concentrations in human plasma and has been successfully applied for pilot pharmacokinetic study which may support dose optimization.