BACKGROUND: Human cerebrospinal fluid (CSF) is often acquired in Phase I clinical trials to assess the CNS penetration of new pharmacological agents and to search for biomarkers associated with PD effects. Robust methods for neurotransmitter metabolites in CSF have proven elusive, in part due to inadequate reversed phase LC retention. RESULTS: Benzoyl chloride derivatization was used to promote retention for LC-MS/MS for a panel of neurotransmitter metabolites while delivering a concise method for sample preparation. CONCLUSION: A validated assay in human CSF was obtained for 3,4-dihydroxyphenylacetic acid, homovanillic acid, 3,4-dihydroxyphenylglycol and 5-hydroxyindoleacetic acid. This method is differentiated from other LC-MS/MS methods by delivering results in line with full regulatory expectations.
BACKGROUND:Human cerebrospinal fluid (CSF) is often acquired in Phase I clinical trials to assess the CNS penetration of new pharmacological agents and to search for biomarkers associated with PD effects. Robust methods for neurotransmitter metabolites in CSF have proven elusive, in part due to inadequate reversed phase LC retention. RESULTS:Benzoyl chloride derivatization was used to promote retention for LC-MS/MS for a panel of neurotransmitter metabolites while delivering a concise method for sample preparation. CONCLUSION: A validated assay in human CSF was obtained for 3,4-dihydroxyphenylacetic acid, homovanillic acid, 3,4-dihydroxyphenylglycol and 5-hydroxyindoleacetic acid. This method is differentiated from other LC-MS/MS methods by delivering results in line with full regulatory expectations.
Authors: Sanjay Das; Artem V Trubnikov; Anton M Novoselov; Alexander V Kurkin; Joris Beld; Andrea Altieri; Sandhya Kortagere Journal: ACS Med Chem Lett Date: 2022-09-19 Impact factor: 4.632
Authors: Jenny-Marie T Wong; Paige A Malec; Omar S Mabrouk; Jennifer Ro; Monica Dus; Robert T Kennedy Journal: J Chromatogr A Date: 2016-04-04 Impact factor: 4.601
Authors: Yeow-Kuan Chong; Chi-Chun Ho; Shui-Yee Leung; Susanna K P Lau; Patrick C Y Woo Journal: Comput Struct Biotechnol J Date: 2018-08-28 Impact factor: 7.271