Separation and quantitation of azimilide and its putative metabolites by capillary electrophoresis.

Reliable methods based on capillary electrophoresis (CE) have been developed for the separation and quantitation of azimilide, an antiarrhythmic drug under development at Procter & Gamble Pharmaceuticals (P&GP). Both capillary zone electrophoresis (CZE) and micellar electrokinetic capillary chromatography (MECC) were employed in the separation of azimilide from its impurities, degradants and/or metabolites. Separation of azimilide from NE-11178, F-410, F-1054 and F-1292 was obtained by MECC at pH 9 with 50 mM sodium dodecyl sulfate (SDS). The separation of azimilide and NE-10171, a key metabolite of azimilide, was difficult because their structures differ by only a single methyl group. The best separation was achieved under acidic pH conditions with cetyltriethyl ammonium chloride (CTAC) additive in the buffer. All of the CE separations were completed within a substantially shorter time and with better resolution than the corresponding high-performance liquid chromatography (HPLC) separations. Quantitation was done with azimilide and NE-10171. Calibration curves ranging from 10 to 1000 microg/ml were obtained with R2 greater than 0.997 for both azimilide and NE-10171. The back-calculated concentrations of the calibration standards and the recoveries of the quality control (QC) samples were within the acceptance range currently used for HPLC methods. These results demonstrated the viability of CE as an alternative technique for drug metabolism studies in support of pharmaceutical development.

Xeroradiography of the breast: overview of 21,057 consecutive cases.

Xeroradiography was performed on 21,057 new patients referred over a 5 1/2-year period. For purposes of analysis, mammograms reported as "benign" or "follow-up suggested" were considered negative and those reported as "suspicious" or "strongly suggestive of cancer" were considered positive. All patients were followed up for 12 months. After 6 months, 773 breast cancers were diagnosed. An additional 19 cancers were proved to exist during the 6-12-month period. The cancer rate increased progressively with age and ranged from 1.2% at age 30-39 years, to 4.5% at age 50-59 years, to 11.8% at age 70 years and over. Mammography had a sensitivity of 91.1%, a specificity of 89.9%, and a predictive value of 25.5%. Sensitivity increased with age, ranging from 78.5% at age 30-39 to 95.1% at age 70 and over. Predictive value increased dramatically with age, varying from 12.4% at age 30-39, to 28.4% at age 50-59, to 49.4% at age 70 years and over.

The male breast.

Simultaneous bilateral primary breast carcinoma in the male is a rare occurrence. Prognostic factors determining the survival rate in male patients with breast cancer are the same as for those in female patients. Retraction and bloody discharge from the nipple, enlargement of axillary nodes, ulceration of the skin, and so forth indicate a poor prognosis. Early detection of cancer using the best available modality, therefore, is of great importance in improving the survival of these patients.