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

• Published in: European journal of pharmaceutical sciences Vol. 23; no. 4; pp. 355 - 362
• Main Authors: De Beer, T.R.M., Vergote, G.J., Baeyens, W.R.G., Remon, J.P., Vervaet, C., Verpoort, F.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 01.12.2004; Elsevier
• Subjects: Biological and medical sciences; Chromatography, High Pressure Liquid; FT-Raman spectroscopy; General pharmacology; HPLC; Medical sciences; Medroxyprogesterone Acetate - analysis; Medroxyprogesterone Acetate - standards; Models, Chemical; Pharmaceutical Solutions - analysis; Pharmaceutical Solutions - standards; Pharmaceutical suspension; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Spectrum Analysis, Raman - methods; Spectrum Analysis, Raman - standards; Technology, Pharmaceutical - methods; Validation; Validation; FT-Raman spectroscopy; Pharmaceutical suspension; HPLC; Pharmaceutical technology; Dosage form; HPLC chromatography; Medroxyprogesterone; Suspension; Acetate; Quantitative analysis; Progestagen
• DOI: 10.1016/j.ejps.2004.08.009
• ISSN: 0928-0987

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.