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.
Structural identification of extractables from rubber closures used for pre-filled semisolid drug applicator by chromatography, mass spectrometry, and organic synthesis.
Extractables or leachables from rubber closures used for drug products can potentially be detrimental since some of these rubber extractables are known to be toxic and pyrogenic. In addition, these extractables could interfere with analysis or even affect the stability profile of the active ingredients. For these reasons, it became necessary to identify structures of the possible extractables or leachables from rubber closures so that their potential impact on the drug products that are in direct contact with rubber closures could be evaluated. In this report, five species, 4-(1,1-dimethyl-propyl)-phenol (1), sulfur (2), 2,6-di-tert-butyl-[1,4] benzoquinone (3), furan-2-yl-(5-hydroxymethyl-furan-2-yl)-methanol (4), and 2-bromo-4-(1,1-dimethyl-propyl)-phenol (5), were found to be possible extractables from the rubber closures which were used in a selected pre-filled semisolid drug applicator. A strategy combining HPLC, GC, mass spectrometry, and organic synthesis was utilized.
Electrophysiological Studies of Penticainide (CM 7857), a New Antiarrhythmic Agent, in Mammalian Myocardium
The intracellular electrophysiologic properties of a new antiarrhythmic substance, penticainide, were studied in isolated rabbit, dog, and guinea pig myocardial preparations superfused or perfused with oxygenated Tyrode's solution. “Therapeutic” concentrations of penticainide (1.5 to 3 x 10-5 M) had little effect on sinus node automaticity; sinoatrial conduction was slightly delayed. In atrial, Purkinje and ventricular fibers, amplitude, and maximal rate of rise of phase 0 (dV/dtmax) were decreased by penticainide; Purkinje-ventricle conduction velocity was depressed. Penticainide did not significantly modify action potential duration (APD) of rabbit atria and dog ventricle and reduced APD and effective refractory period (ERP) of dog Purkinje and guinea pig ventricular fibers. Penticainide reduced APD heterogeneity of Purkinje-ventricle junction with a preferential effect at the gate and decreased tension amplitude of perfused papillary muscle in dog heart. The effect of penticainide on dV/dtmax was voltage and rate dependent; the resting block was weak. Thus, penticainide is a class 1 antiarrhythmic agent with properties of class 1B agents such as APD reduction and properties of class 1C agents such as slow recovery kinetic of rate-dependent block.