I-Lin Tsai (Presenter)
Taipei Medical University
Bio: I received my Bachelor¡¦s degree in Pharmacy, from National Taiwan University (NTU) in 2006, and enrolled into the Graduate Institute of Pharmaceutical Science in NTU at the same year. During my Ph.D program, my research mainly focused on efficient pharmaceutical and toxic compounds analysis via development of novel capillary electrophoresis (CE) and LC-MS methods under the guidance of Dr. Kuo, Ching-Hua. During my first two years of postdoctoral research in the Center of Genomic Medicine, NTU, I built up my knowledge in metabolomics study. In the following years, I continued to expand my study discipline to proteomics study since 2013 under the supervision of Dr. Chen, Chung-Hsuan in Academia Sinica, Taiwan. At the end of 2015, I received the faculty position as assistant professor in Taipei Medical University, and is now focusing on LC-MS based clinical applications.
Authorship: Ching-Hua Kuo (1), Hsin-Yu Sun (2), Divyabharathi Chepyala(1), Shu-Wen Lin (1), I-Lin Tsai (3)*
(1) School of Pharmacy, College of Medicine, National Taiwan University, Taiwan (2)Department of Internal Medicine, National Taiwan University Hospital, Taiwan (3) Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei,Taiwan
| Short Abstract Colistin, an old lipopeptide antibiotic with known nephrotoxicity and neurotoxicity is now being used to treat Gram-negative multidrug resistant bacterial infections. To ensure the efficacy and safety of colistin, therapeutic drug monitoring is recommended. Dried blood spot (DBS) has been applied to therapeutic drug monitoring. In this study, we developed an analytical method for determination of colistin from DBS by using liquid chromatography-tandem mass spectrometry. The validated method is efficient and high throughput which shows the potential for therapeutic drug monitoring of colistin. |
Long Abstract
The outbreaks of multidrug resistant (MDR) Gram-negative bacterial infections including MDR Acinetobacter baumannii (MDRAB) and MDR Pseudomonas aeruginosa (MDRPA) have been reported worldwide in recent years. It has been reported that MDRAB and MDRPA infections significantly increase treatment complexity and the duration of hospital stays for patients. In contrast to the progress of new drug development for multidrug resistant Gram-positive infections, few drugs are successfully developed for Gram-negative bacterial infections. Colistin, an old lipopeptide antibiotic with known nephrotoxicity and neurotoxicity, was withdrawn in the 1970s but is now being used to treat Gram-negative MDR strains. To ensure the efficacy and safety of colistin, therapeutic drug monitoring is recommended. Colistin methanesulfonate (CMS) is the inactive prodrug of colistin which is easily hydrolyzed to colisitn in aqueous solution or bio-fluids. Analytical process which is used for therapeutic drug monitoring of colistin needs the consideration for the stability of CMS during preparation and analysis. Dried blood spot (DBS) which provides advantages of small sample volume (< 30 µL whole blood) and analyte stability has been applied to different kinds of clinical applications, such as newborn disease screening and therapeutic drug monitoring. In this study, we developed a sensitive and efficient analytical method for determination of colistin from dried blood spot by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Multiple parameters for sample preparation such as the components of extraction solution, extraction method, and extraction time were optimized. The LC-MS/MS method was validated in terms of intra-day and inter-day precision, accuracy, extraction recovery, and matrix effect. The linearity for quantification of colistin in DBS is between 0.5 to 40 µg mL-1. And the LC-MS analytical time is within 5 min. Compared with plasma or serum, DBS sampling method provides the benefit of stability for CMS where less amount of this prodrug will be hydrolyzed on the dried paper. With the sensitive LC-MS/MS method, few microliters of whole blood are needed from patients. The validated method is efficient and high throughput which shows the potential for therapeutic drug monitoring of colistin in clinical application.
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