• 1.

    US FDA Web site. FDA public health advisory: pergolide (marketed as Permax). Available at: www.fda.gov/cder/drug/advisory/pergolide.htm. Accessed Jun 15, 2008.

  • 2.

    US FDA Center for Veterinary Medicine Web site. CVM update: CVM working to address concerns about supplies of pergolide for horses. Available at: www.fda.gov/cvm/CVM_Updates/pergolide.htm. Accessed Jun 16, 2008.

  • 3.

    United States Pharmacopeia (USP-NF). USP30–NF25. Chapter 795: pharmaceutical compounding—non sterile preparations. In: The United States Pharmacopeia. Rockville, Md: US Pharmacopeial Convention, 2007;330334.

    • Search Google Scholar
    • Export Citation
  • 4.

    Kotzagiorgis ECh, Michaleas S, Antoniadou-Vyza E. Improved photostability indicating ion-pair chromatography method for pergolide analysis in tablets and in the presence of cyclodextrins. J Pharm Biomed Anal 2007;43:13701375.

    • Search Google Scholar
    • Export Citation
  • 5.

    Sprankle DJ, Jensen EC. Pergolide mesilate. In: Britain H, ed. Analytical profiles of drug substances and excipients. Vol 21. New York: Academic Press Inc, 1992;375413.

    • Search Google Scholar
    • Export Citation
  • 6.

    United States Pharmacopeia (USP-NF). USP30–NF25. Official monographs/pergolide. In: The United States Pharmacopeia. Rockville, Md: US Pharmacopeial Convention, 2007;29062907.

    • Search Google Scholar
    • Export Citation
  • 7.

    United States Pharmacopeia (USP-NF). USP30–NF25. Chapter 1191: stability considerations in dispensing practice. In: The United States Pharmacopeia. Rockville, Md: US Pharmacopeial Convention, 2007;655658.

    • Search Google Scholar
    • Export Citation
  • 8.

    Papich MG. Drug compounding for veterinary patients. AAPS J 2005;7:E281E287.

  • 9.

    Yamana T, Tsuji A. Comparative stability of cephalosporins in aqueous solution: kinetics and mechanisms of degradation. J Pharm Sci 1976;65:15631574.

    • Search Google Scholar
    • Export Citation
  • 10.

    European pharmacopoeia. 4.2 ed. Strasbourg, France: Council of Europe, 2003.

  • 11.

    Clemens JA, Okimura T, Smalstig EB. Dopamine agonist activities of pergolide, its metabolites, and bromocriptine as measured by prolactin inhibition, compulsive turning, and stereotypic behavior. Arzneimittelforschung 1993;43:281286.

    • Search Google Scholar
    • Export Citation
  • 12.

    US FDA Center for Veterinary Medicine. Chapter 6, Subchapter 600, Sec. 608.400—compounding of drugs for use in animals, July 2003. In: Compliance policy guide: compliance policy guidance for FDA staff and industry. Rockville, Md: FDA, 2003.

    • Search Google Scholar
    • Export Citation
  • 13.

    Pergolide oral suspension, veterinary. In: The pharmacists' pharmacopeia. 2nd ed. Rockville, Md: US Pharmacopeial Convention, 2008;461.

Advertisement

Effects of compounding and storage conditions on stability of pergolide mesylate

Jennifer L. DavisDepartment of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.

Search for other papers by Jennifer L. Davis in
Current site
Google Scholar
PubMed
Close
 DVM, PhD, DACVIM, DACVCP
,
Loren Madden KirkDepartment of Clinical Pharmacy, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.

Search for other papers by Loren Madden Kirk in
Current site
Google Scholar
PubMed
Close
,
Gigi S. DavidsonDepartment of Clinical Pharmacy, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.

Search for other papers by Gigi S. Davidson in
Current site
Google Scholar
PubMed
Close
 RPh
, and
Mark G. PapichMolecular and Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.

Search for other papers by Mark G. Papich in
Current site
Google Scholar
PubMed
Close
 DVM, MS, DACVCP

Abstract

Objective—To determine the effects of temperature and light over a 35-day period on stability of pergolide mesylate after compounding in an aqueous vehicle.

Design—Evaluation study.

Procedures—Pergolide was compounded into a formulation with a final target concentration of 1 mg/mL. Aliquots of the formulation were then stored at −20°, 8°, 25°, or 37°C without exposure to light or at 25°C with exposure to light for 35 days. Samples were assayed in triplicate by means of high-pressure liquid chromatography immediately after compounding and after 1, 7, 14, 21, and 35 days of storage.

Results—Mean ± SD concentration of pergolide in the formulation immediately after compounding was 1.05 ± 0.086 mg/mL. Samples exposed to light while stored at 25°C had undergone excessive degradation by day 14, samples stored at 37°C had undergone excessive degradation by day 21, and samples stored at 25°C without exposure to light had undergone excessive degradation by day 35. The decrease in expected concentration corresponded with the appearance of degradation peaks in chromatograms and with a change in color of the formulation.

Conclusions and Clinical Relevance—Results indicated that pergolide mesylate was unstable after compounding in an aqueous vehicle and that storage conditions had an effect on stability of the compounded formulation. Compounded pergolide formulations in aqueous vehicles should be stored in a dark container, protected from light, and refrigerated and should not be used > 30 days after produced. Formulations that have undergone a color change should be considered unstable and discarded.

Abstract

Objective—To determine the effects of temperature and light over a 35-day period on stability of pergolide mesylate after compounding in an aqueous vehicle.

Design—Evaluation study.

Procedures—Pergolide was compounded into a formulation with a final target concentration of 1 mg/mL. Aliquots of the formulation were then stored at −20°, 8°, 25°, or 37°C without exposure to light or at 25°C with exposure to light for 35 days. Samples were assayed in triplicate by means of high-pressure liquid chromatography immediately after compounding and after 1, 7, 14, 21, and 35 days of storage.

Results—Mean ± SD concentration of pergolide in the formulation immediately after compounding was 1.05 ± 0.086 mg/mL. Samples exposed to light while stored at 25°C had undergone excessive degradation by day 14, samples stored at 37°C had undergone excessive degradation by day 21, and samples stored at 25°C without exposure to light had undergone excessive degradation by day 35. The decrease in expected concentration corresponded with the appearance of degradation peaks in chromatograms and with a change in color of the formulation.

Conclusions and Clinical Relevance—Results indicated that pergolide mesylate was unstable after compounding in an aqueous vehicle and that storage conditions had an effect on stability of the compounded formulation. Compounded pergolide formulations in aqueous vehicles should be stored in a dark container, protected from light, and refrigerated and should not be used > 30 days after produced. Formulations that have undergone a color change should be considered unstable and discarded.

Contributor Notes

Supported by a grant from the Grayson-Jockey Club Research Foundation Incorporated.

The authors thank Ms. Delta Dise for assistance with sample and data analysis.

Address correspondence to Dr. Davis.