Detection and identification of volatile substances by headspace capillary gas chromatography to aid the diagnosis of acute poisoning.

Headspace gas chromatography with split flame-ionization-electron-capture detection is a simple method of screening for a wide range of volatile substances in biological fluids. A 60 m x 0.53 mm i.d. thick-film (5 microns) fused-silica capillary coated with SPB-1 (Supelchem) with split flame-ionization-electron-capture detection provides a valuable alternative to packed columns in this work. Most commonly abused compounds, including many with very low boiling-points such as bromochlorodifluoromethane (BCF), butane, dimethyl ether, FC 11, FC 12, isobutane and propane, can be retained and differentiated at an initial column temperature of 40 degrees C followed by programming to 200 degrees C. The total analysis time is 26 min. Retention and detector response data were generated for 244 compounds. Good peak shapes are obtained for polar analytes such as ethanol and injections of up to 0.30 cm3 of headspace can be performed with no discernable loss of efficiency. The sensitivity is thus at least as good as that attainable with packed columns. Of the commonly encountered compounds, only isobutane-methanol and paraldehyde-toluene are at all difficult to differentiate. Quantitative measurements can be performed either isothermally or by using the temperature programme.

Rapid high-performance liquid chromatographic methods for the determination of overdose concentrations of some non-steroidal anti-inflammatory drugs in plasma or serum.

Separate methods are described for the determination of the non-steroidal anti-inflammatory drugs diflunisal, indomethacin, fenoprofen, ibuprofen, ketoprofen, naproxen, mefenamic acid and piroxicam at overdose concentrations in human plasma or serum, using high-performance liquid chromatography and ultraviolet detection. A common extraction, involving protein precipitation with acetonitrile, is employed for all methods. A 25 cm Hypersil ODS (5 mu particle size) analytical column is used for all chromatographic separations, with a mobile phase of acetonitrile-acetate buffer (pH 4.2 or 4.8). The methods are all reproducible and can also determine concentrations that fall within the normal therapeutic range for each drug.

The relationship between plasma ibuprofen concentrations and toxicity in acute ibuprofen overdose.

1. The information available from the literature and from a prospective survey of ibuprofen overdose being undertaken by the London centre of the National Poisons Information Service (NPIS) was examined utilizing the Generalized Linear Interactive Modelling (GLIM) statistical computing package. 2. This confirmed that timed ibuprofen plasma concentrations were related to the symptoms of tachycardia, dizziness, tinnitus, ocular symptoms and coma/stupor as well as to reversible renal impairment and plasma hepatic enzyme elevation. 3. The best model of the relationship between symptomatic toxicity and timed ibuprofen plasma concentrations, was an exponential equation in time. Because of the lack of specificity or sensitivity in this model, and absence of demonstrable clinical advantages from its application, we do not recommend its use as a guide to predict toxicity. 4. However analysis of a larger information base utilizing similar methodology could, by increasing the statistical power of the resultant model, provide a useful means of predicting ibuprofen toxicity. 5. A previously postulated relationship between post-ingestion ibuprofen plasma concentrations and toxicity was not confirmed.

Ibuprofen overdose: the first two years of over-the-counter sales.

Experience during 14 years of prescription only use indicates that the non-steroidal anti-inflammatory drug (NSAID) ibuprofen is of low toxicity in acute overdose. In August 1983 ibuprofen was licensed for over-the-counter (OTC) use in the UK and it was recognised that this change could have an impact upon the epidemiology of analgesic overdose in this country. The London centre of the National Poisons Information Service (NPIS) began a new prospective survey of ibuprofen overdose at the time of OTC release. The first 2 years of this survey detected a marked increase in enquiries concerning ibuprofen overdose but there was no evidence to contradict the former claims of low toxicity. The importance of continued monitoring is stressed.

The effect of diflunisal administration on platelet aggregation and cerebral blood flow.

The effect of a high dose of diflunisal (750 mg twice daily) on platelet aggregation and cerebral blood flow was investigated in 8 healthy volunteers. Diflunisal inhibited platelet aggregation consistently; this effect on platelets was reversed within 24 hours after the last dose of diflunisal. There was, however, no correlation between the anti-aggregatory effect of diflunisal and its plasma concentration. Diflunisal did not alter cerebral blood flow.