An Analytical Method for the Analysis of Tulathromycin, an Equilibrating Triamilide, in Bovine and Porcine Plasma and Lung

• Published in: Journal of agricultural and food chemistry 2004-04, Vol.52 (8), p.2179-2191
• Main Authors: Gáler, Diana, Hessong, Scott, Beato, Brian, Risk, James, Inskeep, Philip, Weerasinghe, Chandralal, Schneider, Richard P, Langer, Connie, LaPerle, Jennifer, Renouf, Donald, Bessire, Andrew, Español, Eden, Rafka, Robert, Ragan, Colman, Boettner, Wayne, Murphy, Trisha, Keller, David, Benchaoui, Hafid, Nowakowski, Marcus A
• Format: Article
• Language: English
• Subjects: Animal productions; Animals; Anti-Bacterial Agents - analysis; Anti-Bacterial Agents - blood; Biological and medical sciences; blood plasma; cattle; Cattle - blood; Cattle - metabolism; Chromatography, High Pressure Liquid; Disaccharides - analysis; Disaccharides - blood; Disaccharides - pharmacokinetics; Dose-Response Relationship, Drug; drug residues; Drug Stability; Fundamental and applied biological sciences. Psychology; Heterocyclic Compounds - analysis; Heterocyclic Compounds - blood; Heterocyclic Compounds - pharmacokinetics; Lung - chemistry; lungs; macrolide antibiotics; Mass Spectrometry; pharmacokinetics; Quality Control; Sensitivity and Specificity; swine; Swine - blood; Swine - metabolism; Terrestrial animal productions; Vertebrates
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf0351624

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. Keywords: Triamilide antibiotics; tulathromycin; mass spectrometry; swine; swine plasma; swine lung; cattle; cattle plasma; cattle lung; pharmacokinetics