Characterization and Quantitation of Aprepitant Drug Substance Polymorphs by Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy

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• 作者：Roy Helmy ; George X. Zhou ; Yadan W. Chen ; Louis Crocker ; Tao Wang ; Robert M. Wenslow ; Jr. ; and Anant Vailaya
• 刊名：Analytical Chemistry
• 出版年：2003
• 出版时间：February 1, 2003
• 年：2003
• 卷：75
• 期：3
• 页码：605 - 611
• 全文大小：102K
• 年卷期：v.75,no.3(February 1, 2003)
• ISSN：1520-6882

文摘

In this study, we report the use of attenuated totalreflectance Fourier transform infrared spectroscopy (ATR-FT-IR) for the identification and quantitation of twopolymorphs of Aprepitant, a substance P antagonist forchemotherapy-induced emesis. Mixtures of the polymorph pair were prepared by weight and ATR-FT-IRspectra of the powdered samples were obtained over thewavelength range of 700-1500 cm^-1. Significant spectraldifferences between the two polymorphs at 1140 cm^-1show that ATR-FT-IR can provide definitive identificationof the polymorphs. To investigate the feasibility of ATR-FT-IR for quantitation of polymorphic forms of Aprepitant,a calibration plot was constructed with known mixturesof the two polymorphs by plotting the peak ratio of thesecond derivative of absorbance spectra against the weightpercent of form II in the polymorphic mixture. Using thisnovel approach, 3 wt % of one crystal form could bedetected in mixtures of the two polymorphs. The accuracyof ATR-FT-IR in determining polymorph purity of the drugsubstance was tested by comparing the results with thoseobtained by X-ray powder diffractometry (XRPD). Indeed,polymorphic purity results obtained by ATR-FT-IR werefound to be in good agreement with the predictions madeby XRPD and compared favorably with actual values inthe known mixtures. The present study clearly demonstrates the potential of ATR-FT-IR as a quick, easy, andinexpensive alternative to XRPD for the determination ofpolymorphic identity and purity of solid drug substances.The technique is ideally suited for polymorph analysis,because it is precise, accurate, and requires minimalsample preparation.