title: A validated LC-MS/MS method for neurotransmitter metabolite analysis in human cerebrospinal fluid using benzoyl chloride derivatization.
abstract: 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.
authors.affiliation: Lilly Research Laboratories, Eli Lilly & Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Cox
authors.affiliation: Lilly Research Laboratories, Eli Lilly & Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
authors.forename: Jon P
authors.initials: JP
authors.lastname: Butler
authors.affiliation: Lilly Research Laboratories, Eli Lilly & Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
authors.forename: Barry S
authors.initials: BS
authors.lastname: Lutzke
authors.affiliation: Q2 Solutions BioSciences, Ithaca, NY 14850, USA.
authors.forename: Barry A
authors.initials: BA
authors.lastname: Jones
authors.affiliation: Q2 Solutions BioSciences, Ithaca, NY 14850, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Buckholz
authors.affiliation: Q2 Solutions BioSciences, Ithaca, NY 14850, USA.
authors.forename: Raymond
authors.initials: R
authors.lastname: Biondolillo
authors.affiliation: Lilly Research Laboratories, Eli Lilly & Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
authors.forename: Jayne A
authors.initials: JA
authors.lastname: Talbot
authors.affiliation: Lilly Research Laboratories, Eli Lilly & Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
authors.forename: Eyassu
authors.initials: E
authors.lastname: Chernet
authors.affiliation: Lilly Research Laboratories, Eli Lilly & Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
authors.forename: Kjell A
authors.initials: KA
authors.lastname: Svensson
authors.affiliation: Lilly Research Laboratories, Eli Lilly & Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
authors.forename: Bradley L
authors.initials: BL
authors.lastname: Ackermann
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000134:cerebrospinal fluid / Q000592:standards; D000818:Animals; D001565:Benzoates / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000592:standards; D019963:Clinical Chemistry Tests / Q000379:methods*; D006207:Half-Life; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid / Q000592:standards; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid / Q000592:standards; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000134:cerebrospinal fluid / Q000592:standards; D018377:Neurotransmitter Agents / Q000134:cerebrospinal fluid* / Q000737:chemistry / Q000378:metabolism; D011786:Quality Control; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000592:standards
chemical_list: D001565:Benzoates; D018377:Neurotransmitter Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; C010117:3,4-dihydroxyphenylglycol; C013409:benzoyl chloride; D006719:Homovanillic Acid