GLC determination of butylated hydroxyanisole in human plasma and urine.

A highly sensitive and specific GLC method was developed for the analysis of butylated hydroxyanisole, a commonly used antioxidant. Concentrations below 100 ng/ml could be detected in human plasma and urine. Preliminary pharmacokinetic studies demonstrated that, upon administration of 100 mg po, butylated hydroxyanisole was quickly absorbed and removed from the plasma with a high degree of intersubject variability.

Kinetics of 3-tert-butyl-4-hydroxyanisole (BHA) in man.

High-resolution capillary gas chromatography-mass spectrometry with selective ion monitoring and using deuterated 3-tert-butyl-4-hydroxyanisole (BHA) as an internal standard was used to measure BHA in the plasma and urine of human volunteers after oral administration of 30 or 5 mg of the compound in olive oil. Pharmacokinetic studies showed similar plasma-concentration profiles in subjects treated with either level of BHA. About 20% of the administered dose was excreted as BHA glucuronide in the urine within the first 24 hr.

Disposition of single oral doses of butylated hydroxyanisole in man and rat.

The kinetics and metabolism of butylated hydroxyanisole (BHA) have been compared between man and rats. Oral doses of 2, 20 or 200 mg BHA/kg body weight were administered to male Wistar rats and a single oral dose of 0.5 mg/kg body weight was administered to human volunteers (non-smoking males). Following oral administration of 2 or 20 mg BHA/kg body weight to rats, no plasma BHA profiles were observed, whereas at the 200 mg BHA/kg body weight dose level plasma BHA peak concentrations between 100 and 400 ng/ml were detected. Plasma BHA peak levels and the area under the curve show that the application of 15% polyethylene glycol-400 as the vehicle produced significantly lower values compared with those obtained using the vehicles, salad dressing, corn oil and dimethylsulphoxide. In man, oral administration of 0.5 mg BHA/kg body weight dissolved in corn oil gave plasma BHA peak concentrations of greater value than 100 ng/ml (range 53 to 255 ng/ml). In rats, 24 hr after dosing 2, 20 or 200 mg BHA/kg body weight the mean BHA concentrations in adipose tissue ranged from 0.7 to 6.8 micrograms/g. In man and rats, BHA was O-demethylated to tert-butylhydroquinone (TBHQ). This is the first study to report that TBHQ is an in vivo metabolite of BHA in rats. Within 4 days following oral administration the total recovery of BHA in the urine and faeces of man (0.5 mg BHA/kg body weight) and rats (200 mg BHA/kg body weight) was 49 +/- 7% and 95 +/- 10% (mean +/- SD) respectively. In rats, BHA was excreted in the urine as free BHA (2%), conjugated BHA (48%) and conjugated TBHQ (9%) and in the faeces as free BHA (36%). In man, BHA was excreted in the urine mainly as conjugated BHA (39%) together with smaller amount of conjugated TBHQ (9%); no free BHA was found in the urine or faeces. In man and rats only the fraction of BHA excreted in urine as conjugates of BHA and TBHQ was qualitatively and quantitatively comparable. Results in this study indicate a considerable difference in the biological fate of BHA following oral administration of high and low doses of BHA in rat and man, respectively.

[Microanalytical GCMS method for the assay of the food additive 2-t-butyl-4-methoxyphenol (BHA) in plasma]. / Metodo microanalitico GC/MS per il dosaggio dell'additivo alimentare 2-t-butyl-4-metossifenolo (BHA) nel plasma.

A GC/Ms method is described for the determination of the antioxidant 2-t-butyl-4-methoxyphenol (BHA) in plasma using Sep-Pak C18 cartridges for extraction. Picogram amounts of BHA could be detected in rat plasma with a high degree of specificity, accuracy and significant time and material saving.

Determination of the antioxidant 3-tert.-butyl-4-hydroxy-anisole in rat-plasma using high-resolution gas chromatography-mass spectrometry.

A method is described for the determination of the antioxidant 3-tert.-butyl-4-hydroxy-anisole in rat plasma using high-resolution capillary gas chromatography-mass spectrometry with selective ion monitoring. Following the addition of the isomer 2-tert.-butyl-4-hydroxy-anisole, used as an internal standard, extraction was made with n-hexane and the extract derivatized with heptafluorobutyric anhydride. The gas chromatographic separation was carried out on a SE-52 fused silica capillary column and the derivatized 3-tert.-butyl-4-hydroxyanisole and its isomer detected by recording the intensities of their common fragment ion at m/e 361. The sensitivity of the method allowed the antioxidant to be measured in 0.1-ml rat plasma samples down to a level of 10 ng/ml with a high degree of specificity and accuracy. The method has been applied to a preliminary pharmacokinetic study in rats after oral dosage.