Novel rearrangements of an N-oxide degradate formed from oxidation of a morpholine acetal substance P antagonist.

Compound 1 [5-[2(R)-[1(R)-(3,5-bistrifluoromethylphenyl) ethoxy]-3(s)-(4-fluorophenyl)morpholin-4-ylmethyl]-3h-[1,2,3] triazol-4-ylmethyl]dimethylamine represents a new class of potent, orally active substance P antagonists, which possess a characteristic structural feature-a cis-2-alkoxy-3-arylmorpholine core. The oxidative degradation of 1 in drug substance and formulations was found to occur through the two trialkylamine oxides, which undergo secondary degradations to give rise to observed degradation products. In this study, the five primary degradation products of the N-oxide 2 formed from the oxidation of the morpholine core of 1 were identified by LC/MS and MS/MS.

Identification and quantitation of extractables from cellulose acetate butyrate (CAB) and estimation of their in vivo exposure levels.

The purpose of this study was to qualitatively and quantitatively determine potential cellulose acetate butyrate (CAB) extractables in a way to meaningfully predict the in vivo exposure resulting from clinical administration. Extractions of CAB-381-20 were performed in several solvent systems, consistently resulting in the detection of three extractables. The extractables have been identified as acetic acid, butyric acid, and E-2-ethyl-2-hexenoic acid (E-EHA) by LC/UV, LC/MS and NMR.

Identification by LC/MS(n) of degradates of a novel carbapenem antibiotic in an aqueous matrix.

Increased drug resistance in Staphylcocci and Enterococci to currently available antibiotics has significantly limited therapeutic options. Recently, a novel carbapenem antibiotic (Compound A) with a releasable side chain adjacent to the carbapenem was investigated to combat methicillin- and vancomycin-resistant Staphylococci and vancomycin-resistant Enterococci. The major advantage of Compound A over existing antibiotics can be attributed to the fact that cleavage of the side chain upon beta-lactam ring opening retained anti-bacterial activity while expelling the immunodominant epitope of the presumed beta-lactam hapten.