High-performance liquid chromatographic method for the simultaneous determination of pentisomide and its major metabolite N-desisopropylpentisomide in plasma, urine and tissues using solid-phase extraction.
A rapid, sensitive and selective high-performance liquid chromatographic method for the simultaneous determination of pentisomide and its major metabolite desisopropylpentisomide in plasma, urine and tissues has been developed. The method for plasma samples, urine samples and tissue samples, after homogenizing with 50% ethanol, involves extraction of samples via activated Bond-Elut C8 disposable columns with methanol at pH 10 after addition of internal standard, and initially on column washing of samples at pH 10 with water and acetonitrile. The obtained methanolic extract is evaporated to dryness under nitrogen at 25 degrees C; the sample residue is then reconstituted in mobile phase and an aliquot of this solution is injected into the liquid chromatograph. Separation is performed using a Nova-Pak C18 4 microns particle size column operating in combination with radial compression separation unit and a methanol-water-di-sec.-butylamine-phosphoric acid (40:60:0.5:0.2, v/v) pH 3.5 mobile phase with ultraviolet detection at 258 nm. Endogenous substances or a variety of drugs concomitantly used in pentisomide therapy, with the exception of disopyramide, do not interfere with the assay. The mean recovery of pentisomide and desisopropylpentisomide from plasma and urine and from tissues is more than 91 and 86%, respectively. The limit of detection of the assay is 10 ng/ml for both drugs. The intra- and inter-day coefficient of variation for replicate analyses of spiked plasma samples is less than 7 and 8%, respectively. Mean steady-state plasma levels of pentisomide and desisopropylpentisomide in patients on chronic oral therapy are reported.
Electrophysiologic effects and pharmacokinetics of intravenous penticainide (CM 7857).
Penticainide is a new class I antiarrhythmic agent. Its electrophysiological effects and pharmacokinetic properties were studied in 28 patients undergoing endocavitary exploration for paroxysmal supraventricular tachycardia (10 cases), WPW syndrome involving an accessory pathway (5 cases), and unexplained dizziness (13 cases). Increasing doses of penticainide were infused in the first 18 patients (0.12 up to 3.5 mg kg-1). The next ten patients received 4 mg kg-1 over a 30 minute period. Penticainide shortened the sinus cycle length and increased the transnodal conduction time. The ventricular conduction time tended to increase. Atrial functional refractory period increased when atrioventricular nodal and ventricular refractory periods remained unchanged. In patients with previous supraventricular tachycardias all triggered arrhythmias were prevented with dosages higher than 2 mg kg-1 and related blood levels higher than 3 mg l-1. A dose-dependency of plasma and renal clearance was documented. Average Cmax values after 4 mg kg-1 was 7.37 +/- 1.28 mg l-1. No adverse events occurred during the trial and penticainide proved to be well tolerated.
Understanding of 33 S NMR Shielding in Inorganic Sul fi des and Sulfates
Density functional theory (DFT) calculations of the magnetic shielding in solid state nuclear magnetic resonance (NMR) experiments provide an important contribution for the understanding of the experimentally observed chemical shifts. In this work we focus on the relation between atomic and orbital character of the valence and conduction band wave functions and the S NMR shielding in sulfides and sulfates. This allows us to understand the origin of the observed large (over 1000 ppm) variation of the chemical shifts measured at the sulfur nucleus. We show that the variation of the NMR chemical shifts in sulfides is mostly related to the presence of metal d states and their variation in the energy position within the conduction bands.