Biomaterial Database

A validated LC-MS/MS method for neurotransmitter metabolite analysis in human cerebrospinal fluid using benzoyl chloride derivatization. 2015

Jennifer M Cox, and Jon P Butler, and Barry S Lutzke, and Barry A Jones, and John E Buckholz, and Raymond Biondolillo, and Jayne A Talbot, and Eyassu Chernet, and Kjell A Svensson, and Bradley L Ackermann

Lilly Research Laboratories, Eli Lilly & Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.

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. CONCLUSIONS 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.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008734	Methoxyhydroxyphenylglycol	Synthesized from endogenous epinephrine and norepinephrine in vivo. It is found in brain, blood, CSF, and urine, where its concentrations are used to measure catecholamine turnover.	Hydroxymethoxyphenylglycol,MHPG,MOPEG,Vanylglycol,4-Hydroxy-3-methoxyphenylethylene Glycol,4-Hydroxy-3-methoxyphenylethyleneglycol,4-Hydroxy-3-methoxyphenylglycol,Methoxyhydroxyphenylglycol, (+)-Isomer,Methoxyhydroxyphenylglycol, (+-)-Isomer,Methoxyhydroxyphenylglycol, (-)-Isomer,4 Hydroxy 3 methoxyphenylethylene Glycol,4 Hydroxy 3 methoxyphenylethyleneglycol,4 Hydroxy 3 methoxyphenylglycol
D011786	Quality Control	A system for verifying and maintaining a desired level of quality in a product or process by careful planning, use of proper equipment, continued inspection, and corrective action as required. (Random House Unabridged Dictionary, 2d ed)	Control, Quality,Controls, Quality,Quality Controls
D002851	Chromatography, High Pressure Liquid	Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.	Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D006207	Half-Life	The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity.	Halflife,Half Life,Half-Lifes,Halflifes
D006719	Homovanillic Acid	A 3-O-methyl ETHER of (3,4-dihydroxyphenyl)acetic acid.	3-Methoxy-4-Hydroxyphenylacetic Acid,4-Hydroxy-3-Methoxyphenylacetic Acid,3 Methoxy 4 Hydroxyphenylacetic Acid,4 Hydroxy 3 Methoxyphenylacetic Acid,Acid, 3-Methoxy-4-Hydroxyphenylacetic,Acid, 4-Hydroxy-3-Methoxyphenylacetic,Acid, Homovanillic
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006897	Hydroxyindoleacetic Acid		5-HIAA,5-Hydroxy-3-Indoleacetic Acid,5-Hydroxyindolamine Acetic Acid,5 Hydroxy 3 Indoleacetic Acid,5 Hydroxyindolamine Acetic Acid,Acetic Acid, 5-Hydroxyindolamine,Acid, 5-Hydroxy-3-Indoleacetic,Acid, 5-Hydroxyindolamine Acetic,Acid, Hydroxyindoleacetic
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001565	Benzoates	Derivatives of BENZOIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxybenzene structure.	Benzoate,Benzoic Acids,Acids, Benzoic