title: An analytical method for the analysis of tulathromycin, an equilibrating triamilide, in bovine and porcine plasma and lung.
abstract: Tulathromycin is a novel member of the triamilide class of antibiotics that was developed as a safe and effective single-dose treatment of bovine and porcine respiratory disease. An accurate and precise analytical method was developed for the extraction and measurement of tulathromycin in livestock plasma and lung homogenates. Analytes were solid-phase extracted onto a weak cation exchanger after aqueous dilution of samples and addition of heptadeutero-tulathromycin as an internal standard. Following HPLC with a narrow bore C8 column, quantitative detection of tulathromycin was accomplished by monitoring the transition of a doubly charged precursor ion to a singly charged product ion by tandem mass spectrometry using a triple quadrupole mass spectrometer. Procedures were validated for a dynamic range of 0.1 to 25 ng on column. Observed accuracies were between 90 and 110% of nominal and precision (RSD) varying 7% or less. Response and stability experiments showed that deuterated tulathromycin did not parallel the chemical behavior of tulathromycin. Applicability of the method to livestock studies was tested with plasma and lung samples from cattle and swine dosed with tulathromycin at multiple doses. The results demonstrated that the analytical method performed well in a range of sample concentrations spanning over 3 orders of magnitude and provided dose-exposure relationships for cattle and swine.
authors.affiliation: Pfizer Global Research and Development, Groton Laboratories, Pfizer Inc, Eastern Point Road, Groton, Connecticut 06340, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Gáler
authors.forename: Scott
authors.initials: S
authors.lastname: Hessong
authors.forename: Brian
authors.initials: B
authors.lastname: Beato
authors.forename: James
authors.initials: J
authors.lastname: Risk
authors.forename: Philip
authors.initials: P
authors.lastname: Inskeep
authors.forename: Chandralal
authors.initials: C
authors.lastname: Weerasinghe
authors.forename: Richard P
authors.initials: RP
authors.lastname: Schneider
authors.forename: Connie
authors.initials: C
authors.lastname: Langer
authors.forename: Jennifer
authors.initials: J
authors.lastname: LaPerle
authors.forename: Donald
authors.initials: D
authors.lastname: Renouf
authors.forename: Andrew
authors.initials: A
authors.lastname: Bessire
authors.forename: Eden
authors.initials: E
authors.lastname: Español
authors.forename: Robert
authors.initials: R
authors.lastname: Rafka
authors.forename: Colman
authors.initials: C
authors.lastname: Ragan
authors.forename: Wayne
authors.initials: W
authors.lastname: Boettner
authors.forename: Trisha
authors.initials: T
authors.lastname: Murphy
authors.forename: David
authors.initials: D
authors.lastname: Keller
authors.forename: Hafid
authors.initials: H
authors.lastname: Benchaoui
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Nowakowski
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000032:analysis* / Q000097:blood; D002417:Cattle / Q000097:blood / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004187:Disaccharides / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D006571:Heterocyclic Compounds / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics; D008168:Lung / Q000737:chemistry*; D013058:Mass Spectrometry; D011786:Quality Control; D012680:Sensitivity and Specificity; D013552:Swine / Q000097:blood / Q000378:metabolism*; D018942:Macrolides
chemical_list: D000900:Anti-Bacterial Agents; D004187:Disaccharides; D006571:Heterocyclic Compounds; C485204:tulathromycin; D018942:Macrolides