title: High-throughput bioanalysis of bile acids and their conjugates using UHPLC coupled to HRMS.
abstract: BACKGROUND
  Quantitative assessment of bile acids in biological matrixes is of growing interest, primarily due to hepatic toxicity resulting from drug interactions with the bile salt export pump. Nevertheless, many bile acids demonstrate poor fragmentation in MS, making conventional MS/MS not a good match for their selective quantitation in biological matrices.
  
  
  RESULTS
  The current study was designed to evaluate the feasibility of simultaneous quantitation of 19 bile acids using HRMS coupled to UHPLC separation with minimal instrument optimization. An effective chromatography was developed using an Agilent Zorbax(®) Eclipse XDB-C18 column (1.8 µm, 50 x 2.1 mm internal diameter), achieving separation of 19 compounds in 10 min. Excellent assay reproducibility was demonstrated, with two sets of standard curves, run 42 days apart.
  
  
  CONCLUSIONS
  The results show that LC-HRMS is a viable platform for high throughput bioanalysis of bile acids especially in a drug-discovery setting.
authors.affiliation: Covance Laboratories Inc., 3301 Kinsman Blvd, Madison, WI 53704, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Ding
authors.forename: Eric T
authors.initials: ET
authors.lastname: Lund
authors.forename: John
authors.initials: J
authors.lastname: Zulkoski
authors.forename: John P
authors.initials: JP
authors.lastname: Lindsay
authors.forename: Donald L
authors.initials: DL
authors.lastname: McKenzie
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000302:isolation & purification*; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000592:standards; D000882:Haplorhini / Q000378:metabolism; D057166:High-Throughput Screening Assays / Q000379:methods* / Q000592:standards; D006801:Humans; D057230:Limit of Detection; D013058:Mass Spectrometry / Q000379:methods* / Q000592:standards; D051381:Rats; D012015:Reference Standards; D015203:Reproducibility of Results
chemical_list: D001647:Bile Acids and Salts