Ambiguities in IR and X-ray characterization of amphotericin B

Authors

  • G. Schwartzman,

    Corresponding author
    1. Pharmaceutical Research and Testing, Food and Drug Administration, U.S. Department of Health, Education, and Welfare, Washington, D.C.
    • Pharmaceutical Research and Testing, Food and Drug Administration, U.S. Department of Health, Education, and Welfare, Washington, D.C.
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  • I. Asher,

    1. Office of Science, Food and Drug Administration, U.S. Department of Health, Education, and Welfare, Rockville, Md.
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  • V. Folen,

    1. Division of Drug Chemistry, Food and Drug Administration, U.S. Department of Health, Education, and Welfare, Washington, D.C.
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  • W. Brannon,

    1. Division of Drug Chemistry, Food and Drug Administration, U.S. Department of Health, Education, and Welfare, Washington, D.C.
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  • J. Taylor

    1. National Center for Antibiotics Analysis, Food and Drug Administration, U.S. Department of Health, Education, and Welfare, Washington, D.C
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Abstract

Two distinct IR spectra of amphotericin B have been reported. These differences can be obtained from the same sample by surprisingly small changes in the method of sample preparation. Type I spectra (hand-ground samples) are characterized by a sharp C[TRIPLE BOND]O stretching band at 1692 cm−1, and Type II spectra (vibrator-ground samples) are characterized by a broad C[TRIPLE BOND]O stretching band near 1710 cm−1. X-ray powder diffraction demonstrates that vibrator grinding promotes a transition from a crystalline to an amorphous phase. The two phases are not bioequivalent. Differential thermal analysis reveals a transition near 157°, and samples heated to 158° give only Type II IR spectra. However, a marked color change accompanies such heating (i.e., structural changes affecting the chromophore have been thermally induced), while X-ray spectra show an increase of only about 30% in amorphous content. Furthermore, hand-ground samples heated to 120° still display only Type I IR spectra. Thus, the vibrator-induced transition is not solely a static thermal effect. Many observed spectral lines can be assigned to specific functional groups.

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