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Evaluation of an extractionless high-performance liquid chromatography-tandem mass spectrometry method for detection and quantitation of rosiglitazone in canine plasma

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  • 1 Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.
  • | 2 Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.
  • | 3 Department of Veterinary Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.
  • | 4 Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.
  • | 5 Department of Veterinary Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.
  • | 6 Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.
  • | 7 Department of Veterinary Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.

Abstract

Objective—To develop a simple extractionless method for detection of rosiglitazone in canine plasma and test the method in a pharmacokinetic study after oral administration of rosiglitazone in dogs.

Animals—3 client-owned dogs with cancer.

Procedures—High-performance liquid chromatography-tandem mass spectrometry was performed on canine plasma. The 3 dogs with cancer in the pharmacokinetic study were assessed via physical examination and clinicopathologic evaluation and considered otherwise healthy. Food was withheld for 12 hours, and dogs were administered a single dose (4 mg/m2) of rosiglitazone. Plasma was collected at various times, processed, and analyzed for rosiglitazone.

Results—The developed method was robust and detected a minimum of 0.3 ng of rosiglitazone/mL. Mean ± SD maximum plasma concentration was 205.2 ± 79.1 ng/mL, which occurred at 3 ± 1 hours, and mean ± SD elimination half-life was 1.4 ± 0.4 hours. The area under the plasma rosiglitazone concentration-versus-time curve varied widely among the 3 dogs (mean ± SD, 652.2 ± 351.3 ng/h/mL).

Conclusions and Clinical Relevance—A simple extractionless method for detection of rosiglitazone in canine plasma was developed and was validated with excellent sensitivity, accuracy, precision, and recovery. The method enabled unambiguous evaluation and quantitation of rosiglitazone in canine plasma. This method will be useful for pharmacokinetic, bioavailability, or drug-drug interaction studies. Oral rosiglitazone administration was well tolerated in the dogs.

Contributor Notes

Supported by the University of California-Davis Center for Companion Animal Health Grant #2007-45-R. Ms. Guerrero was supported by the Toni Wiebe Memorial Research Fund.

Address correspondence to Dr. Rodriguez (dvmrodriguez@ucdavis.edu).