Development of dried plasma spot-based tandem mass spectrometry assay for simultaneous monitoring of pyrazinamide and its metabolites in tuberculosis patients

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题名:	Development of dried plasma spot-based tandem mass spectrometry assay for simultaneous monitoring of pyrazinamide and its metabolites in tuberculosis patients
作者:	WANAHARI, TENRI ASHARI
贡献者:	國際醫學研究碩士學位學程李枝新蔡伊琳
关键词:	pyrazinamide;tuberculosis;therapeutic drug monitoring;mass spectrometry;dried plasma spot pyrazinamide;tuberculosis;therapeutic drug monitoring;mass spectrometry;dried plasma spot
日期:	2024-07-12
上传时间:	2024-11-06 13:33:48 (UTC+8)
摘要:	Monitoring pyrazinamide (PZA) and its metabolites during anti-TB treatment is important to prevent PZA-associated liver injury. This study explores the potential of using liquid chromatography-tandem mass spectrometry (LC-MS/MS) combined with dried plasma spots (DPS) as an assay for simultaneous measurement of PZA and its three metabolites, i.e., pyrazinoic acid (POA), hydroxypyrazinamide (OH-PZA), and hydroxypyrazinoic acid (OH-POA). The DPS method employed a micro-sampling strategy, requiring a 15 μL of plasma volume for each sample. Sample extraction from DPS was achieved using a 40 second of 400-watt microwave-assisted process with 60% methanol solution. All analytes were separated with a C18 column (100 mm × 2.1 mm, 2.6 μm, 100 ?). A multiple reaction monitoring detection was used with positive electrospray ionization mode. The correlation coefficients of the calibration curves were > 0.999 for all analytes. The quantification ranges were 0.31 to 120 μg/mL for PZA, and 0.06 to 24 μg/mL for POA, OH-PZA, and OH-POA. Intra-assay precision (n=5) exhibited a maximum relative standard deviation (RSD) of 3.00% and a minimum of 0.7%, with accuracy ranging from 89.2% to 113.1%. Inter-assay precision ranged from 1.5% to 12.1% of RSD, with accuracy between 95.1% and 111.8% (n=3). Following validation, we applied the developed method to 35 paired DPS and plasma samples from five TB patients for therapeutic drug monitoring and pharmacokinetic study. Plasma and DPS showed a high correlation with correlation of coefficients (rho) were 0.988, 0.994, 0.993, and 0.995 for PZA, POA, OH-PZA, and OH-POA, respectively. This method has the potential to significantly benefit TB patients management for personalized PZA treatment. Monitoring pyrazinamide (PZA) and its metabolites during anti-TB treatment is important to prevent PZA-associated liver injury. This study explores the potential of using liquid chromatography-tandem mass spectrometry (LC-MS/MS) combined with dried plasma spots (DPS) as an assay for simultaneous measurement of PZA and its three metabolites, i.e., pyrazinoic acid (POA), hydroxypyrazinamide (OH-PZA), and hydroxypyrazinoic acid (OH-POA). The DPS method employed a micro-sampling strategy, requiring a 15 μL of plasma volume for each sample. Sample extraction from DPS was achieved using a 40 second of 400-watt microwave-assisted process with 60% methanol solution. All analytes were separated with a C18 column (100 mm × 2.1 mm, 2.6 μm, 100 ?). A multiple reaction monitoring detection was used with positive electrospray ionization mode. The correlation coefficients of the calibration curves were > 0.999 for all analytes. The quantification ranges were 0.31 to 120 μg/mL for PZA, and 0.06 to 24 μg/mL for POA, OH-PZA, and OH-POA. Intra-assay precision (n=5) exhibited a maximum relative standard deviation (RSD) of 3.00% and a minimum of 0.7%, with accuracy ranging from 89.2% to 113.1%. Inter-assay precision ranged from 1.5% to 12.1% of RSD, with accuracy between 95.1% and 111.8% (n=3). Following validation, we applied the developed method to 35 paired DPS and plasma samples from five TB patients for therapeutic drug monitoring and pharmacokinetic study. Plasma and DPS showed a high correlation with correlation of coefficients (rho) were 0.988, 0.994, 0.993, and 0.995 for PZA, POA, OH-PZA, and OH-POA, respectively. This method has the potential to significantly benefit TB patients management for personalized PZA treatment.
描述:	碩士指導教授：李枝新共同指導教授：蔡伊琳口試委員：李枝新口試委員：蔡伊琳口試委員：白冠壬口試委員：莊永坤口試委員：余明治
附注:	論文公開日期：2029-07-19
数据类型:	thesis
显示于类别:	[國際醫學研究碩博士學位學程] 博碩士論文

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