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Determination and pharmacokinetic study of 1‐ p ‐(3.3‐dimethyl‐1‐triazeno) benzoic acid in cancer patients by capillary gas chromatography
Author(s) -
Li AiQun,
Zhao XiangLan
Publication year - 2001
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.39
Subject(s) - chemistry , chromatography , benzoic acid , pharmacokinetics , flame ionization detector , gas chromatography , urine , detection limit , analytical chemistry (journal) , organic chemistry , medicine , biochemistry
Abstract A capillary gas chromatographic method was developed for determining 1‐ p ‐(3.3‐dimethyl‐1‐triazeno) benzoic acid in the plasma and urine of cancer patients under pharmacokinetic study. The drug was extracted with ethyl acetate and methylated with diazomethane. Octadelane (10 µg/ml) was added as internal standard. The separation was carried out on an OV‐1 quartz capillary column, 15 m × 0.32 mm (0.52 µm), with high‐purity nitrogen as carrier gas and flame ionization detector (FID) as detector. The column temperature was held at 130°C for 9 min and then programed to 240°C, at a rate of 35°C/min. The temperature of both injector and detector was 260°C. The standard curve was linear from 0.4 to 40 µg/mL in plasma, and from 0.8 to 20 µg/mL in urine, with correlation coefficients of 0.9979 and 0.9932. The relative standard deviations (RSD) were less than 9.7%. The minimum recovery of this method was 81.8%. This method was applied to the pharmacokinetic studies of 1‐ p ‐(3.3‐dimethyl‐1‐triazeno) benzoic acid in cancer patients after a single dose (i.v.) of 160, 420 or 760 mg/m 2 was administered. They all conformed to the two‐compartment open model and showed linear pharmacokinetics. The excretion of this drug in the urine was minimal. Copyright © 2001 John Wiley & Sons, Ltd. Abbreviations used: AUC area under the curveDTIC dacarbazineMTD maximum tolerance dosageP‐COOH‐DMT 1‐ p ‐(3.3‐dimethyl‐1‐triazeno) benzoic acidRSD relative standard deviation.