Electrochemical oxidation of CBS-113 A, a new anti-inflammatory drug: applicability to liquid chromatography-electrochemical detection.

The electrochemical properties of a new non-steroidal anti-inflammatory drug (2-hydroxy-4-methylphenyl-2-aminothiazole hydrochloride; CBS-113 A) have been studied using voltammetry in direct current and cyclic modes at glassy carbon disk electrodes. The results show an oxidative process with a diffusion-controlled and a reversible mechanism; these data agree with those obtained in a reversed-phase high-performance liquid chromatography (HPLC) system coupled either with amperometric (single glassy carbon electrode) or coulometric detection (two porous graphite electrodes in series) set at potentials of +0.65 V (vs. Ag/AgCl) and +0.4 V (vs. Pd/H2), respectively. Similar electrochemical properties were found for 2-hydroxyphenyl-2-amino-5'-methylthiazole hydrochloride (RD-1546) which is a potential internal standard. An HPLC system coupled with a UV detector (lambda = 272 nm) and an amperometric detector (+0.65 V) showed a gain in sensitivity of about 10 using electrochemical detection (ED) for the determination of CBS-113 A in human plasma. Linearity range, precision and accuracy were calculated and showed the potential application of HPLC-ED to pharmacokinetic studies of CBS-113 A in plasma.

Individual degradation rate constants for cefotaxime, deacetylation profile.

The individual degradation rate constants for cefotaxime in aqueous solution were calculated within a pH range of 1.6-10.0 at 37 degrees C from high performance liquid chromatography data. This allowed the general degradation profile of cefotaxime to be decomposed into a degradation profile attributed to the opening of the beta-lactam nucleus and a degradation profile attributed to the deacetylation. From the calculations of the individual rate constants, the activity of degraded cefotaxime solutions could be predicted. In the pH range of injectable solutions of cefotaxime 5-7, roughly equivalent amounts of inactive beta-lactam cleavage products and deacetylated compound which has a different spectrum of antibacterial activity are formed.

Determination of aminoglycosides in pharmaceutical formulations--II. High-performance liquid chromatography.

A post-column derivatization procedure using OPA and fluorescence detection has been used for the determination of seven aminoglycosides (dibekacin, framycetin, kanamycin, netilmicin, sisomicin, tobramycin and gentamicin) in commercial pharmaceutical formulations. The linearity, precision and detection limits were satisfactory. Recoveries from eye drops, ointments, injections and capsules were comparable (P = 0.05) to those obtained with TLC or microbiological assays. A ruggedness test showed that the method was not sensitive to minor variations in the mobile phase composition, post-column derivatization system or detection wavelength.

Overlapping ionization constants for cefotaxime.

The attribution of three ionization constants (2.1, 3.4, and 10.9) for cefotaxime has been made, based on potentiometric titration and UV absorption data simultaneously. Two overlapping constants were found (2.1 and 3.4) and attributed to the carboxyl group in the 4 position and to the aminothiazole nucleus, respectively.

Sulpiride pharmacokinetics in humans after intramuscular administration at three dose levels.

Pharmacokinetics of the disinhibitory psychotropic agent sulpiride was investigated in 9 healthy male subjects after intramuscular administrations of 50, 100, and 200 mg in a 3 X 3 Latin square design. Plasma and urine concentrations were measured by HPLC for 36 and 48 h, respectively. The lowest detectable concentration was 10 ng/mL. Plasma concentration versus time and urinary excretion rate versus time curves were consistent with an open two-compartment body model, where mean +/- SD apparent half-lives of the absorption from muscle, lambda 1 distribution, and lambda 2 elimination phases were 6.96 +/- 2.64 min, 0.220 +/- 0.120 h, and 6.74 +/- 2.67 h, respectively. The initial volume of distribution was 0.145 +/- 0.063 L/kg, the steady-state volume of distribution was 0.639 +/- 0.184 L/kg, and the total clearance was 89.8 +/- 22.3 mL/min. The microscopic rate constants were k12 = 2.53 +/- 1.13 h-1, k21 = 0.674 +/- 0.197 h-1, and k10 = 0.635 +/- 0.298 h-1. Comparison of total clearance (89.8 mL/min), renal clearance (83.0 mL/min), and renal clearance of unbound drug (97.6 mL/min, f = 0.15) indicated that sulpiride is mainly excreted unchanged by the renal route, 93.1 +/- 6.6% of the administered dose being recovered unchanged in urine. Statistical evaluation of all the above parameters, determined at the three dosage levels, did not show any variations related to dose; the pharmacokinetics of sulpiride, over the dose range tested, was therefore linear and independent of dose. The two-compartment body model proposed was validated by digital computer simulation on a small digital computer (32K).