Development and validation of a direct, non-destructive quantitative method for medroxyprogesterone acetate in a pharmaceutical suspension using FT-Raman spectroscopy

Eur J Pharm Sci. 2004 Dec;23(4-5):355-62. doi: 10.1016/j.ejps.2004.08.009.

Abstract

A simple linear regression method was developed and statistically validated for the direct and non-destructive quantitative analysis--without sample preparation--of the active pharmaceutical ingredient (API) medroxyprogesterone acetate (MPA) in an aqueous pharmaceutical suspension (150 mg in 1.0 ml) using FT-Raman spectroscopy. The linear regression was modelled by plotting the highest peak intensity of the vector normalized spectral band between 1630 and 1590 cm-1 against different MPA standard suspension concentrations. At this band, no spectral interferences from additives in the suspension are observed. The validated model was used for the quantification of a commercial suspension (150 mg in 1.0 ml) of the commercialized preparations. The same standards and samples were used, respectively, for the development and validation of a simple linear regression model and for the quantitative determination by means of HPLC-with sample preparation-as described for the related substances of MPA in the Ph. Eur. IV. The quantification results obtained by the FT-Raman method corresponded with the claimed label concentration (150.01+/-0.96 mg/ml (n=6)). Applying the HPLC method, however, a systematic error was observed (157.77+/-0.94 mg/ml (n=6)). The direct FT-Raman method hence appears the most reliable for the quantification of the MPA component in suspension, compared to the HPLC method that requires sample preparation. The latter method provides a systematic error because the exact volume or density of a suspension sample is unknown. A precise isolation of fixed volumes from a suspension is rather unfeasible because of the continuous sagging of the suspended particles and their sticking to the used materials in the isolation process.

Publication types

  • Validation Study

MeSH terms

  • Chromatography, High Pressure Liquid
  • Medroxyprogesterone Acetate / analysis*
  • Medroxyprogesterone Acetate / standards*
  • Models, Chemical
  • Pharmaceutical Solutions / analysis
  • Pharmaceutical Solutions / standards
  • Spectrum Analysis, Raman / methods*
  • Spectrum Analysis, Raman / standards
  • Technology, Pharmaceutical / methods*

Substances

  • Pharmaceutical Solutions
  • Medroxyprogesterone Acetate