Determination of the new aromatic retinoic acid Ro 13-7410 in plasma by two-dimensional gas chromatography negative ion chemical ionization mass spectrometry with selected-ion monitoring.
A highly sensitive and specific method for the determination of the aromatic retinoic acid Ro 13-7410 in plasma at the picogram per millilitre level is described. The method involves extraction of plasma using Extrelut-1 columns, purification of the extract with Bond Elut-NH2 cartridges, derivatization with pentafluorobenzyl bromide, and subsequent analysis by two-dimensional capillary gas chromatography using the zone-cutting technique, stable isotope dilution and selective negative ion monitoring chemical ionization mass spectrometry. A tetradeuterated analogue is used as internal standard. Quantification is possible down to 25 pg/ml using 1 ml of plasma. The coefficients of variation of the method as calculated from quality control samples are 8.5 and 4.2% at the 100 and 400 pg/ml levels. The method has been applied to the analysis of plasma of volunteers following an oral dose of 40 micrograms Ro 13-7410 and plasma of dogs following an intravenous and oral dose of 25 and 50 micrograms, respectively.
Pharmaceutical, Department F. Hoffmann-La Roche & Co. Ltd, Basle, Switzerland.
H J
HJ
Egger
U B
UB
Ranalder
E U
EU
Koelle
M
M
Klaus
D000818:Animals; D001565:Benzoates / Q000097:blood*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004285:Dogs; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007202:Indicators and Reagents; D007536:Isomerism; D007553:Isotope Labeling; D012176:Retinoids / Q000097:blood*
D001565:Benzoates; D007202:Indicators and Reagents; D012176:Retinoids; C038864:4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid