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J C Bignall

Publications and source records attributed to J C Bignall.

6 recordsLinked to original sources

Direct quantitative determinations by multiple metastable peak monitoring. 1--Warfarin in plasma.

A technique for the direct quantitative determination of plasma warfarin concentrations has been developed using multiple metastable peak monitoring on a double focusing mass spectrometer of normal geometry. The method uses a direct insertion probe and requires no sample purification or derivatization. Deuterated warfarin was added as an internal standard, and the first field free region metastable fragmentations for the loss of an acetyl radical from the molecular ion of both warfarin and internal standard were monitored. These independent daughter ions were focused by a simple combination of linking the magnetic and electric sectors, accelerating voltage switching and selected ion monitoring using standard instrumentation. Results were acquired and processed by normal selected ion monitoring software. Repeated determinations of plasma warfarin concentrations were made with plasma extracts representing approximately 4 microliter of plasma, each sample taking two minutes to process by this technique.

Humans↗

N-hydroxyphenacetin, a new urinary metabolite of phenacetin in the rat.

N-Hydroxyphenacetin has been found in the urine of rats dosed with phenacetin, extending previous reports that phenacetin is N-hydroxylated by liver microsomes in vitro. After an oral dose of phenacetin (500 mg/kg) urine was collected for 24 hr, conjugates hydrolyzed with extract of Helix pomatia, and the metabolites extracted with dichloromethane and treated with diazomethane. Methylation of N-hydroxyphenacetin produced a stable derivative, N-methoxyphenacetin, which was separated from most other metabolites by thin layer chromatography. Identification of N-methoxyphenacetin was by combined gas chromatography-mass spectrometry and comparison with the synthetic reference compound. Quantification by gas chromatography with flame-ionization detection showed that 0.023% of the dose phenacetin was recovered from urine as N-hydroxyphenacetin. It is probable that this value considerably underestimates the extent of phenacetin N-hydroxylation in vivo, inasmuch as N-hydroxyphenacetin is known to be rapidly degraded in biological systems.

Animals↗