W. Snedden

Maternal and neonatal disposition of pethidine in childbirth—A study using quantitative gas chromatography-mass spectrometry

Abstract An assay for pethidine using gas chromatography-mass spectrometry with single ion monitoring has been developed for its analysis in the blood of neonates whose mothers received pethidine during childbirth. Concentrations were determined from the height of the peak at m/e 218 derived from pethidine compared with that at m/e 234 derived from the internal standard lignocaine. Results from 10 mothers and their babies show the time-related passage of pethidine across the placenta. The elimination half-life of the drug from neonatal blood was 22.7h compared with 3h in the adult.

The measurement of urinary digoxin and dihydrodigoxin by radioimmunoassay and by mass spectroscopy

A radioimmunoassay for urinary digoxin is described which includes an initial solvent extraction to remove factors in urine which cause non-specific interference in the assay. The recoveries obtained using different solvents are compared and the non-specific factors influencing the assay investigated further. These effects were overcome by the use of a small urine volume (10 mul) in a direct, unextracted, urine assay and the results obtained correlated closely with those from the assay using prior extraction (r=0.99). No false positive results were obtained with unextracted urine samples from hospitalised patients not receiving digoxin. The specificity was also determined with regard to the natural steroids, spironolactone and the metabolites of digoxin including dihydrodigoxin. The metabolite dihydrodigoxin, with a saturated lactone ring, was not detected whereas the mono-, and bis-digitoxo-sides and digoxigenin metabolites did cross react in the assay. It was not possible to separate dihydrodigoxin and digoxin by thin-layer chromatography or solvent extraction due to their similar structures, however, mass spectroscopy was successful in this respect and was employed to obtain the ratio of dihydrodigoxin to digoxin in extracted urine samples. Levels of urinary digoxin excreted by patients maintained on different oral doses of the drug were measured. The percentage excreted in the urine as digoxin correlated closely with the oral dose (r = 0.96) but was found to be lower than that reported in most previous studies. Mass spectroscopy measurements showed that an average of 16.4% (range 12.2-19.7%) of the total oral dose was excreted as dihydrodigoxin in the urine of nine patients investigated.

A gas chromatography-mass spectrometry method for the quantitative analysis of melatonin in plasma and cerebrospinal fluid.

Abstract A method has been developed for the quantitative analysis of melatonin in human plasma and cerebrospinal fluid. The technique involves a simple one-step extraction with chloroform and conversion of the melatonin in the extract to its N-trimethylsilyl derivative, which is then measured by means of high-sensitivity gas chromatography—mass spectrometry. Intra-assay precision for triplicate samples at the 20-pg/ml level was better than 20%, while the interassay precision for separate determinations made over the course of a week was better than 18%. In a series of human plasma samples taken over several times during a 24-hr period, a significant increase in melatonin level was noted during the hours of darkness.

Massive excretion of 2-oxoglutaric acid and 3-hydroxyisovaleric acid in a patient with a deficiency of 3-methylcrotonyl-CoA carboxylase

A three-month old child, presenting with a history of feeding problems, suspected respiratory infection and failure to thrive, later developed fits and a profound irreversible metabolic acidosis. Chromatographic investigation of the urine revealed a gross excretion of 2-oxoglutaric and 3-hydroxyisovaleric acids. The identity of these two acids was confirmed by mass spectrometry. Enzyme studies on liver obtained at post-mortem demonstrated a deficiency of 3-methylcrotonyl-CoA:carbon dioxide ligase (ADP) (EC 6.4.1.4).

Urolithiasis due to 2,8-dihydroxyadenine in an adult.

CARTIER and Hamet1 described a patient with calculi formed by 2,8-dihydroxyadenine in 1974. Such calculi are positive for uric acid with standard wet chemistry tests.2 The poorly soluble purine 2,8...

The occurrence and identification of o-hydroxyhippuric acid (salicyluric acid) in the urine of sick children

O-Hydroxyhippuric acid has been identified in the urine of a number of sick children who were not receiving salicylate-containing drugs. Characterisation was effected by thin-layer and gas-liquid chromatography and by gas-liquid chromatography-mass spectrometry. An association between gastro-intestinal dysfunction and the excretion of o-hydroxyhippuric acid was observed in approximately 50% of the patients who excreted this substance.

The use of high resolution mass spectrometry to study purine metabolism in pigs

Abstract Guanine and the xanthine oxidase inhibitor, allopurinol, were administered orally to pigs. The treatments included both separate and combined use of the drugs for varying periods. By means of high resolution mass spectrometry the concentrations of xanthine, hypoxanthine, uric acid, allopurinol, oxipurinol and guanine were measured in samples of kidney, synovial membrane, skeletal muscle and blood plasma from the slaughtered pigs. All tissues were essentially normal except the kidneys from pigs fed both drugs and no accumulation of guanine was observed in either skeletal muscle or synovial membrane tissue. These results are discussed in relation to leg weakness and “guanine gout” in pigs.