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 role of sentinel lymph node biopsy in the management of breast cancer.

Axillary nodes status is the best single predictor of disease outcome in patients with breast cancer; presence ofaxillary node metastasis (ANM) reduces the patient's 5-year survival by 28-40%. However, ANM is seen in only 40% of all breast cancer and furthermore since axillary lymph node dissection (ALND) is associated with significant morbidity, sentinel lymph node biopsy (SLNB) seems to be a good alternative for nodal staging in breast cancer. Pathologically negative sentinel lymph node (SLN) is able to predict the absence of metastasis to the remainder of the regional lymph node basin with a very high degree of certainty. This article presents a systematic detailed review of the existing studies on SLNB in relation to the following parameters: sensitivity and accuracy of the different techniques used; pathologic evaluation of SLN; clinical and pathological factors affecting SLN status and role of SLNB in different clinical situations related to breast cancer management. We have also included brief mention of our experience at UMass from a pathological perspective in this review article.