Complete 1 H, 13 C, and 15 N assignments of the minor isomer of codeine N-oxide.

Codeine N-oxide 2 is an active metabolite of codeine obtained by oxidation and observed as a degradant in codeine drug products such as syrups. Oxidation of codeine's N-methyl function can deliver two regio-isomers due to chirality of the tetra-substituted nitrogen. Hydrogen peroxide oxidation of codeine was performed and induced two different isomers in a 9:1 ratio; these isomers were isolated using preparative high performance liquid chromatography (HPLC) and fully characterized by nuclear magnetic resonance (NMR) techniques. We describe the complete assignment of the minor isomer of codeine N-oxide 3 and attribute a (S) configuration (N-methyl axial) of the tetra-substituted nitrogen. The effects of N-oxidation on the 15 N chemical shifts of the codeine are presented. The 15 N shifts were determined using the CIGAR-HMBC experiment at natural abundance, and the nitrogen resonance of codeine shifted downfield from 42.8 to 118.7 ppm for both N-oxide isomers.

Development of an HPLC/UV method for the evaluation of extractables and leachables in plastic: Application to a plastic-packaged calcium gluconate glucoheptonate solution.

Calcium gluconate glucoheptonate (GGCa) is known to interact with glass containers, leading to the leaching of aluminum from the glass into the solution at toxic level. Therefore, plastic containers seem to be a preferable packaging alternative. Nevertheless, plastics contain potentially toxic additives which could be released into the solution. In order to study content container interaction between GGCa and two plastic containers (polypropylene PP and polyethylene PE containers), an HPLC-PDA method was developed to separate, detect and quantify eleven additives commonly found in plastic materials, with good limit of detection and quantification. This method was then applied to evaluate the compatibility between GGCa and the two plastic containers. After 3 months of storage at 25 °C, none of the eleven additives were detected in GGCa solutions. The safety concern threshold (SCT) and of the analytical evaluation threshold (AET) were evaluated to discriminate the need to identify and qualify unknown peaks.