Identification and characterization of new degradation products of cefepime dihydrochloride monohydrate drug substance during stress stability studies.

The degradation products of Cefepime dihydrochloride that emerged throughout stress stability studies have been determined, identified and characterized. The two new impurities were detected by gradient reverse-phase high performance liquid chromatography (HPLC), and Impurity-I was formed in the range from 0.2 to 11.0% and Impurity-II range from 0.2 to 3.5%. These impurities have been identified by LC/MS, and were not reported in the literature. These impurities were synthesized, isolated and characterized. Based on the spectral data, the impurities were named (6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-(methoxyimino)acetamido]-3-[(1-methyl-1-pyrrolidinium)methyl]-3-cephem-4-carboxylate-1-oxide (Impurity-I); (2RS)-2[[(Z)-2-(2-amino-4-thiazolyl)-2-(methoxyimino)acetamido]-methyl]-1,2,5,7-tetrahydro-7-oxo-4H-furo[3,4-d][1,3]thiazine (Impurity-II). The structures were established unambiguously by independent synthesis and co-injection in HPLC to confirm the retention times and relative retention times. The structural elucidation of these impurities by spectral data ((1)H NMR, (13)C NMR, 2D-NMR (COSY, HSQC and HMBC), LC/MS, TOF-MS, elemental analysis and IR), synthesis, isolation and the formation of these impurities are discussed in detail.

Angioplasty of tortuous left internal mammary artery: description of a new technique.

Angioplasty of the distal anastomosis site of a markedly tortuous left internal mammary artery (LIMA)--anterior descending artery is described. Tortuosity of LIMA was negotiated using the Tracker-Seeker catheter guidewire system. Angioplasty was then performed using the conventional technique.

Treadmill exercise during adenosine infusion is safe, results in fewer adverse reactions, and improves myocardial perfusion image quality.

BACKGROUND: Combining low-level treadmill exercise with adenosine infusion may result in fewer bradyarrhythmic complications by increasing sympathetic tone and may improve myocardial perfusion image quality by decreasing background activity. METHODS: Patients referred for outpatient pharmacologic stress myocardial perfusion imaging performed simultaneous treadmill exercise (mean 2.2 metabolic equivalents) throughout 6-minute adenosine infusion (adenosine-exercise n = 507). Patients unable to exercise and those with left bundle branch block received adenosine infusion alone (adenosine-nonexercise n = 286). Adverse reaction data were collected on all patients and compared by sex. Background-to-target activity was calculated in a blinded fashion on 200 randomly selected patients. RESULTS: During the period from April 1996 to December 1998, 507 patients (64%) underwent adenosine-exercise testing, whereas 286 (36%) underwent adenosine-nonexercise testing. Hypotensive and arrhythmic (atrioventricular block, sinus bradycardia, and new onset atrial fibrillation or flutter) adverse reactions occurred less often during adenosine-exercise than during adenosine-nonexercise. Neither death nor myocardial infarction occurred in either group. In the adenosine-exercise group, 2.8% of patients experienced an adverse reaction versus 5.6% of the adenosine-nonexercise group (P = .04). The reduction in adverse reactions occurred in both men and women, although women had significantly more adverse reactions than men (5.7% vs 1.8%, P = .004). Liver/heart and gut/heart ratios were lower in the adenosine-exercise group (1.05+/-0.42 vs. 1.21+/-0.55 , P = .01; 0.61+/-0.21 vs. 0.69+/-0.24, P = .03, respectively). CONCLUSIONS: Compared with adenosine infusion alone, combining low-level treadmill exercise with adenosine in outpatients is safe, better tolerated, and improves image quality. Women were more likely to experience adverse reactions than men.