Analyses of marketplace tacrolimus drug product quality: Bioactivity, NMR and LC–MS

•Tacrolimus capsules from five sources have similar biological potencies.•All tacrolimus products inhibit the calcineurin/IL-2 pathway with similar efficacies.•Any ascomycin is below the detection limits of both NMR or LC–MS.•No other literature predicted impurities were observed in the marketplace...

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Bibliographic Details
Published in:Journal of pharmaceutical and biomedical analysis 2013-11, Vol.85, p.108-117
Main Authors: Sommers, Cynthia D., Pang, Eric S., Ghasriani, Houman, Berendt, Robert T., Vilker, Vincent L., Keire, David A., Boyne, Michael T.
Format: Article
Language:English
Subjects:
Ascomycin
Chromatography, Liquid - methods
Drug Contamination
Drug product impurities
Drug product quality
Generic drugs
Immunosuppression
Magnetic Resonance Spectroscopy - methods
Mass Spectrometry - methods
Tacrolimus - analysis
Tacrolimus - pharmacology
Tacrolimus - standards
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Summary:•Tacrolimus capsules from five sources have similar biological potencies.•All tacrolimus products inhibit the calcineurin/IL-2 pathway with similar efficacies.•Any ascomycin is below the detection limits of both NMR or LC–MS.•No other literature predicted impurities were observed in the marketplace products. Tacrolimus (FK506) is a potent, narrow therapeutic index, immunosuppressive drug used to avoid organ rejection in patients that have undergone organ transplantation. Recent clinical reports suggested a significant reduction in the tacrolimus concentration/dose ratio in the plasma of liver and kidney recipients when the reference listed drug was substituted with a generic drug. In response to these concerns about switching between tacrolimus from different approved manufacturers during treatment, the FDA initiated purity, potency and quality studies of the innovator and generic tacrolimus products available in the US marketplace. A combination of analytical methods, including mass spectrometry (LC–MS), nuclear magnetic resonance (NMR) and bioactivity assay were developed and validated to assess the quality of tacrolimus. These tests measured the identity, impurities and activity of tacrolimus from active pharmaceutical ingredient (API) sources and with formulated drug product from five different approved manufactures. In addition, some testing was performed on tacrolimus capsules obtained from a non US approved Indian source. The data obtained showed no discernible difference in the impurity profiles and potency between the generic and innovator tacrolimus products.
ISSN:0731-7085
1873-264X
DOI:10.1016/j.jpba.2013.07.001