Quantitative analysis of 3-isopropylamino-1,2-propanediol as a degradation product of metoprolol in pharmaceutical dosage forms by HILIC-CAD / 药物分析学报

Aryloxypropanolamine is an essential structural scaffold for a variety of β-adrenergic receptor antago-nists such as metoprolol. Molecules with such a structural motif tend to degrade into α, β-hydroxypropanolamine impurities via a radical-initiated oxidation pathway. These impurities are typically polar and nonchromophoric, and are thus often overlooked using traditional reversed phase chromatography and UV detection. In this work, stress testing of metoprolol confirmed the generation of 3-isopropylamino-1,2-propanediol as a degradation product, which is a specified impurity of metoprolol in the European Pharmacopoeia (impurity N). To ensure the safety and quality of metoprolol drug products, hydrophilic interaction chromatography (HILIC) methods using Halo Penta HILIC column (150 mm×4.6 mm, 5 μm) coupled with charged aerosol detection (CAD) were developed and optimized for the separation and quantitation of metoprolol impurity N in metoprolol drug products including metoprolol tartrate injection, metoprolol tartrate tablets, and metoprolol succinate extended-release tablets. These HILIC-CAD methods were validated per USP validation guidelines with respect to speci-ficity, linearity, accuracy, and precision, and have been successfully applied to determine impurity N in metoprolol drug products.

Structural confirmation of sulconazole sulfoxide as the primary degradation product of sulconazole nitrate / 药物分析学报

Sulconazole has been reported to degrade into sulconazole sulfoxide via sulfur oxidation; however, structural characterization data was lacking and the potential formation of an N-oxide or sulfone could not be excluded. To clarify the degradation pathways and incorporate the impurity profile of sulconazole into the United States Pharmacopeia–National Formulary (USP–NF) monographs, a multifaceted approach was utilized to confirm the identity of the degradant. The approach combines stress testing of sulco-nazole nitrate, chemical synthesis of the degradant via a hydrogen peroxide-mediated oxidation reaction, semi-preparative HPLC purification, and structural elucidation by LC―MS/MS and NMR spectroscopy. Structural determination was primarily based on the comparison of spectroscopic data of sulconazole and the oxidative degradant. The mass spectrometric data have revealed a McLafferty-type rearrange-ment as the characteristic fragmentation pathway for alkyl sulfoxides with aβ-hydrogen atom, and was used to distinguish the sulfoxide from N-oxide or sulfone derivatives. Moreover, the generated sulco-nazole sulfoxide was utilized as reference material for compendial procedure development and valida-tion, which provides support for USP monograph modernization.

The Deep Inferior Epigastric Perforator and Pedicled Transverse Rectus Abdominis Myocutaneous Flap in Breast Reconstruction: A Comparative Study

BACKGROUND: Our objective was to compare the complication rates of two common breast reconstruction techniques performed at our hospital and the cost-effectiveness for each test group. METHODS: All patients who underwent deep inferior epigastric perforator (DIEP) flap and transverse rectus abdominis myocutaneous (TRAM) flap by the same surgeon were selected and matched according to age and mastectomy with or without axillary clearance. Patients from each resultant group were selected, with the patients matched chronologically. The remainder were matched for by co-morbidities. Sixteen patients who underwent immediate breast reconstruction with pedicled TRAM flaps and 16 patients with DIEP flaps from 1999 to 2006 were accrued. The average total hospitalisation cost, length of hospitalisation, and complications in the 2 year duration after surgery for each group were compared. RESULTS: Complications arising from both the pedicled TRAM flaps and DIEP flaps included fat necrosis (TRAM, 3/16; DIEP, 4/16) and other minor complications (TRAM, 3/16; DIEP, 1/16). The mean hospital stay was 7.13 days (range, 4 to 12 days) for the pedicled TRAM group and 7.56 (range, 5 to 10 days) for the DIEP group. Neither the difference in complication rates nor in hospital stay duration were statistically significant. The total hospitalisation cost for the DIEP group was significantly higher than that of the pedicled TRAM group (P<0.001). CONCLUSIONS: Based on our study, the pedicled TRAM flap remains a cost-effective technique in breast reconstruction when compared to the newer, more expensive and tedious DIEP flap.