NIR Spectrometry Reveals Lack of Content Uniformity in Methylprednisolone Sodium Succinate

近红外光谱分析揭示琥珀酸甲泼尼龙钠含量不均匀

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Abstract

Methylprednisolone sodium succinate for injection, USP is an anti-inflammatory glucocorticoid. The active ingredient is methylprednisolone sodium succinate, which is the sodium succinate ester of methylprednisolone. The substance is a white or nearly white, odorless, hygroscopic, amorphous solid. It is highly soluble in water and alcohol, insoluble in chloroform, and only slightly soluble in acetone. This injectable form of the drug is indicated for the treatment of various conditions, including some allergic states, dermatologic, endocrine, gastrointestinal, hematologic, neoplastic, nervous system, ophthalmic, renal, respiratory, and rheumatic disorders. The analysis of a single lot of methylprednisolone sodium succinate revealed significant intra-lot variability in the near-infrared spectra. Differences were visually apparent in the absorbance peaks, particularly in the ranges of 4500 to 5000 cm(-1) and 6000 to 6500 cm(-1). Further examination of a zoomed-in region (7000 to 8500 cm(-1)) showed two spectra that were statistically significant outliers, positioned at 4.4 and 5.9 standard deviations (SDs) from the center of the sample cluster. An analysis of a spectral library containing 242 vials of methylprednisolone sodium succinate from 26 different lots found significant interlot variability and statistically confirmed the presence of distinct subclusters. To statistically validate the visual findings, a subcluster detection algorithm was applied to the spectral data. The algorithm confirmed that two distinct groups exist within the spectral data. The measured correlation value (r(ts) =0.8704) was below the 98% confidence level threshold (r(tn) =0.9916), leading to the acceptance of the alternative hypothesis that more than one group is present.

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