Gas chromatographic determination of guanadrel in plasma and urine.

To evaluate the pharmacokinetics and drug availability from various dosage formulations, a method for the determination of guanadrel, (1,4-dioxaspiro[4,5]dec-2-ylmethyl)guanidine, in plasma and urine was required. A gas chromatographic procedure, based on formation of a hexafluoroacetylacetone derivative in a two-phase system of water and toluene, was developed. The limit of determination of the method is 5 ng/ml guanadrel in plasma and 15 ng/ml guanadrel in urine. Statistical analyses indicate average recoveries of 98.1 +/- 18.0 and 104.4 +/- 15.6% from plasma and urine, respectively. Mass spectrometric analyses, in conjunction with gas chromatography, confirmed the specificity of the method for intact drug. The procedure was applied successfully to drug absorption studies in humans.

Isomeric inversion of ibuprofen (R)-enantiomer in humans.

Enantiomeric compositions of the major urinary metabolites of ibuprofen [(RS)-2-(4-isobutylphenyl)propionic acid]were characterized after oral administration of the racemic mixture and oral administration of the individual enantiomers to normal human volunteers. Resolution of the diastereomeric amides, formed by reaction of the urinary metabolites with (S)-(-)-alpha-methylbenzylamine, was achieved by GLC. Only the (R)-(-)-enantiomer of the intact drug was inverted to its optical antipode, (S)-(+), in humans. However, both (S)-(+)- and (R)-(-)-enantiomers of the intact drug were transformed independently in vivo to the major metabolites, i.e., 2,4'-(2-hydroxy-2-methylpropyl)phenylpropionic acid and 2,4'-(2-carboxypropyl)phenylpropionic acid. In vivo metabolism of ibuprofen to its carboxy metabolite was not stereoselective.

GLC determination of ibuprofen [dl-2-(p-isobutylphenyl) propionic acid] enantiomers in biological specimens.

To study the behavior of the d- and l-isomers of ibuprofen in humans, a method for the determination of the individual enantiomers in plasma and urine was required. A specific procedure was developed based on (a) benzene extraction of the acidified specimens, (b) TLC of the benzene extract residue, (c) formation of the l-alpha-methylbenzylamides of the materials eluted from the chromatograms, and (d) quantification of the resulting diastereoisomeric amides by GLC in conjunction with flame-ionization detection. When using a 1-ml aliquot of the specimen, the method is sensitive to 1 mug of each enantiomer/ml of plasma or urine. As compared to simple aqueous solutions, the average recoveries of the enantiomers from plasma and urine ranged from 94 to96%. Mass spectrometric analyses, in conjunction with GLC, confirmed the specificity of the method for the intact enantiomers. The procedure was applied successfully to drug absorption studies in humans. After oral administration of the racemic mixture, the predominant enantiomer in peripheral circulation and excreted in urine was of the d-configuration.