HPLC determination of rubber septum contaminants in the iodinated intravenous contrast agent (sodium iothalamate).
A simple and rapid method is described for the determination of 2-mercaptobenzothiazole and mercaptobenzothiazole disulfide leached from rubber closures into the iodinated contrast medium (sodium iothalamate). The contaminants were extracted with methylene chloride and analyzed by high-performance liquid chromatography using ultraviolet detection at wavelengths of 272 and 328 nm. The structures of the impurities were confirmed unequivocally by mass spectrometry. The minimum detectable level was 1 microgram/100 mL (0.01 ppm). The quantitation of contaminants leached from rubber stoppers provides a means for evaluating possible health risks of the extractables.
Leaching of 2-(2-hydroxyethylmercapto) benzothiazole into contents of disposable syringes.
A contaminant was found to leach into the contents of two brands of disposable syringes. It was identified as 2-(2-hydroxyethylmercapto) benzothiazole and is believed to be formed during manufacture of the syringes as a result of a reaction between 2-mercaptobenzothiazole, a rubber vulcanization accelerator, and ethylene oxide, used for sterilization. The contaminant was isolated form the rubber plunger-seal and identified using mass, NMR, and UV spectroscopic methods. The amount of contaminant appearing in the contents of syringes was measured; up to 140 micro g was found under clinically relevant conditions. This finding has important implications with respect to the use of these syringes for drug administration and for the collection of blood for drug analyses.
High-performance liquid chromatographic analysis of cefotetan epimers in human plasma and urine.
Cefotetan, a new broad-spectrum 7 alpha-methoxycephalosporin antibiotic, was assayed in plasma and urine by means of reversed-phase high-performance liquid chromatography. Commercially available cefotetan exists in two epimeric forms. The procedure described allows the separation and quantitation of both epimers. For the first time a different pharmacokinetic behaviour (t1/2 = 3 h versus 4 h) for each epimer after intravenous injection to healthy volunteers is demonstrated. It is assumed that one epimer is bound to a greater extent to serum proteins and is therefore responsible for the differences observed. As both epimers exhibit similar antibacterial activity, it seems doubtful whether these differences would have clinical significance. Iothalamic acid was determined simultaneously as a marker of kidney function.