Quantitative analysis of 6,11-dihydro-11-oxo-dibenz[b,e] oxepin-2-acetic acid (isoxepac) in plasma and urine by gas--liquid chromatography.

A method is described for the quantitative analysis of 6,11-dihydro-11-oxo-dibenz[b,e]-oxepin-2-acetic acid (isoxepac) in plasma and urine. Isoxepac and internal standard was analysed by gas-liquid chromatography using a flame ionization detector. The method is accurate and precise over the range 0.1--30 microgram/ml. The method has been applied to the analysis of plasma and urine from both healthy volunteers and patients receiving therapeutic oral doses of isoxepac.

Gas-liquid chromatographic determination of 1,3-dihydro-3-phenylspiro(isobenzofuran-1,4-piperidine), HP 505, in biological fluids using a nitrogen-specific detector.

A gas chromatographic method for the determination of 1,3-dihydro-3-phenylspiro[isobenzo-1,4-piperidine], HP 505, in plasma red blood cells and urine has been developed. HP 505 and internal standard are extracted from basified fluid with hexane and then back extracted into acetic acid. After re-extraction into hexane, HP 505 and internal standard are analysed by gas-liquid chromatography as the N-propionyl derivatives using a nitrogen-specific detector. Concentrations of HP 505 can be measured over the range 2-100 ng/ml plasma. The method has been applied to the analysis of biological fluids from volunteers receiving oral doses of HP 505.

Determination of oxpentifylline and a metabolite, 1-(5'-hydroxyhexyl)-3,7-dimethylxanthine, by gas--liquid chromatography using a nitrogen-selective detector.

A gas chromatographic method for the determination of oxpentifylline and a metabolite, 1-(5'-hydroxyhexyl)-3,7-dimethylxanthine is described. Oxpentifylline, metabolite and internal standard are extracted from basified plasma into dichloromethane, then the metabolite and internal standard are converted to their O-trifluoroacetates. Analysis by gas--liquid chromatography using a nitrogen-selective detector allows quantification of oxypentifylline and 1-(5'-hydroxyhexyl)-3,7-dimethylxanthine down to levels of 3 ng/ml and 3--10 ng/ml, respectively. The assay had been applied to plasma samples from volunteers after both intravenous and oral administration of oxpentifylline. The need to separate plasma from erythrocytes immediately after venipuncture sampling to prevent further metabolism of oxpentifylline is emphasized.

Quantitative analysis of tiamenidine in human plasma by gas chromatography mass spectrometry of a dibenzyl derivative.

A gas chromatography mass spectrometry method has been developed and evaluated for the quantitative analysis of tiamenidine in plasma. Tiamenidine and internal standard are extracted from basified plasma, converted to dibenzyl derivatives by reaction with benzyl bromide and potassium t-butoxide in the presence of 18-crown-6 ether prior to analysis by selected ion monitoring. The method can be used over the range 0.2--10 ng ml-1 with a coefficient of variation of better than 20% at 1 ng ml-1.

Metabolism and pharmacokinetics of 14C-pentoxifylline in healthy volunteers.

The metabolism and pharmacokinetics of 14C-pentoxifylline (Trental) have been studied in three healthy male volunteers after oral administration of 200 mg (50 microCi). The radiolabelled drug was rapidly absorbed and by 6 h 89.1 +/- 2.4% of the 14C material was excreted in the urine. The dosed 14C material (96.9 +/- 2.2%) was recovered in excreta by 24 h with 93.3 +/- 2.3% in the urine 3.0 +/- 0.2% in the faeces. Peak plasma levels of radioactivity (4.1-6.2 micrograms eq ml-1) occurred 0.25-0.75 h after administration. This radioactivity decayed in a biexponential fashion with an initial half-life of 1.01 +/- 0.13 h and a terminal half-life of 36.06 +/- 16.94 h. The peak plasma levels (0.48-2.25 micrograms ml-1) of parent drug, as measured using a specific gas chromatographic assay also occurred at 0.25-0.75 h and subsequently decayed extremely rapidly with an initial half-life of 0.18 +/- 0.15 h and terminal half-life of 0.76 +/- 0.44 h. Urinary 14C-labelled metabolites were separated by semi-preparative high performance liquid chromatography and characterised by mass spectrometry and by comparison with authentic synthetic compounds. Of the dosed 14C-pentoxifylline, greater than 90% could be identified as characterised metabolites in urine.

Concentration dependence of the order-disorder transition of carrageenans. Further confirmatory evidence for the double helix in solution.

The temperature-induced changes in optical rotation which are associated with the order-disorder transition of carrageenans have been analysed to investigate the concentration dependence and hence to attempt to derive the number of polysaccharide chains involved in the ordered species at equilibrium. The consequences of the known polydispersity have been analysed by computer-modelling and it is shown that this need not cause misleading results. For iota-carrageenan segments of 0.1 M NaCl and 0.1 M KCl solution the results point to a two-chain state and therefore support the proposed double helix model. For chi-carrageenan segments the apparent average number of molecules involved in the ordered state at equilibrium is 3.7, suggesting that if double helices form here they aggregate further. The method of investigation may be generally applicable to measuring the number of chains which associate in ordered states in aqueous solutions of polysaccharides.

The pharmacokinetics of oxpentifylline in man when administered by constant intravenous infusion.

Subjects were each given either a 25, 50 or 100 mg intravenous loading dose of oxpentifylline followed by an intravenous infusion at a constant rate of 1.5 mg/min for 3 h. Plasma levels of oxpentifylline were measured to obtain information on its pharmacokinetics and to establish which of the loading doses gave the most rapid attainment of the steady state plasma levels of intact drug. Oxpentifylline kinetics were best described by a two compartment model giving a characteristic dip in the plasma level versus time curves before steady state was reached when either the 50 or 100 mg loading doses, followed by the constant intravenous infusion, were given. The terminal half-life of oxpentifylline was 1.02 +/- 0.86 h, reflecting a very high clearance of the drug (approx. 3 000 to 6 000 ml/min). The high clearance could be attributed to extrahepatic metabolism occurring in blood which was observed in vitro using whole blood but not plasma. The clearance of a reduced metabolite of oxpentifylline was less than that of the intact drug, although the half-life was similar (0.83 +/- 0.18 h). Of the three loading doses tested, only the highest showed any side effects, these being transient and occurring within a 5 to 10 min period after dosing and appeared to correlate with the high initial plasma levels of the drug. The 25 mg loading dose gave initial plasma levels generally below the final steady state levels, whilst the 50 mg loading was the closest to giving immediate steady state plasma levels of oxpentifylline.