title: Raman spectroscopic method for the determination of medroxyprogesterone acetate in a pharmaceutical suspension: validation of quantifying abilities, uncertainty assessment and comparison with the high performance liquid chromatography reference method.
abstract: An alternative fast and non-destructive validated Raman spectroscopic analytical procedure, requiring no sample preparation, was compared with the industrially applied HPLC reference method (Pfizer Manufacturing Belgium) for the quantitative determination of medroxyprogesterone acetate (MPA) in DepoProvera suspensions (150 mg mL(-1), Pfizer). The Raman calibration model was developed by plotting the peak intensity of the baseline-corrected and normalized spectral band (corrected by external standard measurements) between 1595 and 1620 cm(-1) against known MPA concentrations in standards. At this band, no spectral interferences from the suspension medium are observed. The most suitable model for the calibration data (straight line or higher order polynomial) was determined by evaluating the fit and predictive properties of the models. In a second step, the developed Raman spectroscopic analytical method was validated by calculating the accuracy profile on the basis of the analysis results of validation samples. Furthermore, based on the data of the accuracy profile, the measurement uncertainty was determined. Finally, as the aim of the alternative method is to replace the destructive, time-consuming HPLC method, requiring sample preparation, it needs to be demonstrated that the new Raman method performs at least as good as the HPLC method. Therefore, the performance (precision and bias) of both methods was compared. A second order polynomial calibration curve through the calibration data supplies the best predictive properties and gives an acceptable fit. From the accuracy profile, it was concluded that at the target concentration (150 mg mL(-1)), 95 out 100 future routine measurements will be included within the acceptance limits (5%). Comparison of the alternative method with the reference method at the target concentration indicates that the Raman method performs at least as good as the HPLC method for precision (repeatability and intermediate precision) and bias. The fast and non-destructive Raman method hence provides an alternative for the destructive and time-consuming HPLC procedure.
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: W R G
authors.initials: WR
authors.lastname: Baeyens
authors.forename: A
authors.initials: A
authors.lastname: Vermeire
authors.forename: D
authors.initials: D
authors.lastname: Broes
authors.forename: J P
authors.initials: JP
authors.lastname: Remon
authors.forename: C
authors.initials: C
authors.lastname: Vervaet
mesh_terms: D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D017258:Medroxyprogesterone Acetate / Q000032:analysis*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012015:Reference Standards; D015203:Reproducibility of Results; D013059:Spectrum Analysis, Raman / Q000379:methods*
chemical_list: D004364:Pharmaceutical Preparations; D017258:Medroxyprogesterone Acetate