Determination of indomethacin in serum and urine by electron-capture gas-liquid chromatography.

A specific and sensitive method for the quantitative determination of indomethacin in serum and urine is described. The drug is extracted at pH 5.0 with 1,2-dichloroethane and a portion of the organic extract is concentrated and made to react with diazoethane in diethyl ether. The ethyl ester derivative is analyzed by electron-capture gas-liquid chromatography, quantitation being achieved by comparison of peak areas for samples and standards, which are prepared in serum or urine and treated in the same manner as the samples. The limit of sensitivity is 50 ng/ml and the relative standard derivation for repeat determinations on the same sample is about 3%.     

Determination of bromhexine as its trifluoroacetyl derivative by gas-liquid chromatography with electron-capture detection

A specific gas-liquid chromatographic method with electron-capture detection is described for the determination of bromhexine at the nanogram level. Structurally analogous internal standards were synthesized and their suitability was investigated, based on their chromatographic properties on different stationary liquid phases. The electron-capture activity of the compounds is increased by trifluoroacetylation. Reaction conditions for this derivatization were studied. Calibration graphs in the range 0-57 ng (in a total of 100 microliters of reaction mixture) showed good linearity.     

Determination of estradiol 2- and 4-hydroxylase activities by gas chromatography with electron-capture detection

A highly sensitive assay has been developed for measuring the rate of formation of 2-hydroxyestradiol and 4-hydroxyestradiol from estradiol by microsomal preparations. Catechol estrogens were converted to heptafluorobutyryl esters, which were separated by capillary column gas chromatography and quantified using electron-capture detection. 2-Hydroxyestradiol 17-acetate was used as an internal standard. The identity of catechol estrogen derivatives was verified by gas chromatography-mass spectrometry using negative-ion chemical ionization. Estrogens were identified by negative molecular ions and/or by characteristic fragments. This procedure permits quantification of catechol estrogens at the subpicogram level. The assay was validated by comparing estrogen 2- and 4-hydroxylase activities in microsomes from hamster and rat liver with values reported previously.     

Determination of valproic acid (dipropylacetic acid) in plasma by gas-liquid chromatography.

A specific and sensitive procedure for the determination of valproic acid at therapeutic concentrations in human plasma has been developed. The method involves a microscale extraction of the drug from acidified plasma into chloroform. Caproic acid is added as internal standard. The extract is subsequently analysed on a gas chromatography fitted with a flame ionisation detector, and quantitation achieved by the relative-peak-height technique.     

Determination of 4-methyl-cis-hexahydrophthalic anhydride in human blood by gas chromatography with electron-capture detection.

A gas-chromatographic technique using 63Ni electron-capture detection was applied to the determination of 4-methyl-cis-hexahydrophthalic anhydride in the blood of workers occupationally exposed to this airborne agent. The detection limit was 0.24 nmol ml-1. For occupational exposure to between 0.14 and 0.31 mg m-3 of the anhydride, the anhydride concentration in the workers' blood samples ranged from 3.4 to 10.7 nmol ml-1. The results are consistent with earlier findings in animal exposure experiments and support the view that the hydrolysis of the anhydride in a biological medium is not spontaneous, but might be an enzyme-catalysed reaction. The resulting dicarboxylic acid is excreted by the kidneys without further conjugation reactions.     

Determination of gas-liquid partition coefficients by gas chromatography

This review covers theoretical principles and experimental procedures for the determination of gas-liquid partition coefficients, KL, by gas chromatography. In order to precisely define the relationship between KL, retention time and experimental parameters, the retention theory, both for ideal and for imperfect gas phase, is expounded. The most important sources of systematic error, as peak asymmetry, mixed retention mechanisms, column hold-up time and stationary phase mass determination, are discussed. Although the review is focussed on packed columns, comparison to capillary columns is discussed in those aspects in which these last show advantages.     

Determination of sterically hindered phenols by gas-liquid chromatography

Conclusions The possibility has been shown and the optimum conditions have been found for the identification of various 4-alkyl-2,6-di-tert-butylphenols by gas-liquid chromatography on the stationary liquid phases poly(ethylene glycol adipate) and Apiezon-L deposited on Celite C22.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 7, pp. 1618–1622, July, 1970.     

Determination of 4-hydroxyandrostenedione in plasma and urine by extractive alkylation and electron-capture gas chromatography

A sensitive and specific quantitative assay has been developed for the determination of 4-hydroxyandrostenedione (4-OHA), a potent aromatase inhibitor used in the treatment of estrogen-dependent breast cancer. This steroid has a high first-pass metabolism and is extensively metabolized, mainly by glucuronidation. Plasma levels of unchanged 4-OHA are very low, even after high peroral doses. The analytical method is based on the addition of 17 alpha-ethinylestradiol (internal standard), liquid-liquid extraction from biological material followed by extractive alkylation with pentafluorobenzyl bromide and quantitation by gas chromatography. The method has been validated for sensitivity, accuracy and precision and was found to be suitable for application to pharmacokinetic and bioavailability studies of peroral formulations of 4-OHA.