A fast HPLC method for the determination of the oxygen heterocyclic compounds of citrus essential oils was developed. Five different oils were analyzed under identical conditions, by reversed-phase HPLC with photodiode array detector, for a direct comparison of the composition of their oxygen heterocyclic fraction. Analysis time was 7 min. The oils analyzed were lemon, bergamot, mandarin, sweet orange, and bitter orange. The method developed is good for rapid screening or fingerprinting of these essential oils; a slightly slower method is recommended for higher resolution and better quantitative results.

The protein-binding characteristics of the angiotensin II receptor antagonist valsartan were determined in vitro by equilibrium dialysis, using 14C-labeled valsartan with serum from healthy donors, plasma from patients who had received valsartan, serum or plasma from animals, and purified human plasma proteins. The binding of valsartan was high (96 +/- 2%) in human serum at concentrations ranging from 0.05 micrograms/mL to 5 micrograms/mL. A comparable extent of binding (85-99%) was recorded in plasma from patients after repeated administration of valsartan. Albumin (binding 92%) is the main protein involved in the binding to plasma proteins, while the binding to alpha 1-acid glycoprotein was low (22%) and to gamma globulins, negligible. Although highly bound, valsartan was not displaced in vitro by hydrochlorothiazide, diclofenac, furosemide, and warfarin. A high extent of binding was found in rat, dog, and rabbit serum and in marmoset plasma, while a lower binding was found in mouse serum.

An automated analytical method utilizing laboratory robotics has been developed and validated for quantifying concentrations of a new antiepileptic drug candidate (CGP 33101) in human plasma. The robotic system aliquots the biological sample, adds the internal standard (CGP 23901) and pH 12 buffer, extracts the compounds from the basified matrix into an organic phase (methyl-t-butyl ether:dichloromethane, 2:1) and concentrates the extracts for reversed-phase, high performance liquid chromatographic (HPLC) analysis. The robotic system is directly interfaced with the HPLC system. Separation is achieved on a Hypersil 3 microns C18 column (4.6 x 50 mm) with ultraviolet detection of the analytes at 230 nm. Specificity was demonstrated by the lack of interfering peaks at the retention times for both the drug and internal standard. Recovery and reproducibility assessments indicated good accuracy (overall mean relative recovery of 102.7%) and precision (coefficient of variation of 4.4 to 7.7%) for CGP 33101 over the concentration range of 50-4000 ng/mL. The limit of quantification (LOQ) is 50 ng/mL. The method has been successfully applied to a clinical study in which normal volunteers received single oral doses of 400-1200 mg of this new drug candidate.

No abstract

No abstract