title: Development and validation of a direct, non-destructive quantitative method for medroxyprogesterone acetate in a pharmaceutical suspension using FT-Raman spectroscopy.
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.
authors.affiliation: Laboratory of Drug Quality Control, Department of Pharmaceutical Analysis, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium.
authors.forename: T R M
authors.initials: TR
authors.lastname: De Beer
authors.forename: G J
authors.initials: GJ
authors.lastname: Vergote
authors.forename: W R G
authors.initials: WR
authors.lastname: Baeyens
authors.forename: J P
authors.initials: JP
authors.lastname: Remon
authors.forename: C
authors.initials: C
authors.lastname: Vervaet
authors.forename: F
authors.initials: F
authors.lastname: Verpoort
mesh_terms: D002851:Chromatography, High Pressure Liquid; D017258:Medroxyprogesterone Acetate / Q000032:analysis* / Q000592:standards*; D008956:Models, Chemical; D019999:Pharmaceutical Solutions / Q000032:analysis / Q000592:standards; D013059:Spectrum Analysis, Raman / Q000379:methods* / Q000592:standards; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D019999:Pharmaceutical Solutions; D017258:Medroxyprogesterone Acetate