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Biomedical subjects

W Snedden

Publications and source records attributed to W Snedden.

At least 37 records · Page 2Linked to original sources

Specific HPLC assay for serum nifedipine.

A method has been devised for the sensitive, specific and reproducible estimation of nifedipine in human serum. The assay is based on reverse-phase HPLC of an ether extract of serum at pH 9 using nisoldipine as internal standard. The two compounds are detected and quantitated by spectrophotometry at 350 nm. The mean recovery of nifedipine added to blank serum (60-250 ng/ml) was 70%, with a minimum detectable level of 10 ng/ml. Replicate determinations of patients' serum nifedipine (90-150 ng/ml) yielded coefficients of variation of 3.3%. Twelve drugs and non-prescription medicaments which could be ingested at the same time as nifedipine were assessed for interference with the assay but none were found to do so. The rates of absorption and peak serum levels of nifedipine were compared in normo- and hypertensive subjects who received sublingually a single 10 mg dose of the drug. Half the subjects displayed mean maximum serum levels of 148 +/- 34 ng/ml while the other half achieved only 48 +/- 15 ng/ml. The times required to reach those peak levels varied from 30 min to greater than 60 min. These results suggest that the rate of absorption of this drug varies widely among individuals. No significant differences were observed between the normo- and hypertensive groups.

Chromatography, High Pressure Liquid↗

Familial hypertryptophanemia, tryptophanuria and indoleketonuria.

Two patients presenting with mental subnormality and severe emotional lability were examined for possible inborn errors of metabolism. Amino acid and organic acid analyses of their plasma and urine revealed a novel and grossly abnormal metabolism of tryptophan. Basal levels of plasma tryptophan were ten times that of controls and the 24-hour urinary excretion of tryptophan was up to 50 times greater than normal. Both patients excreted about 100 times the normal amounts of indoleacetic, indolelactic and indolepyruvic acids. Administration of oral antibiotic to one of the patients to eliminate intestinal bacteria did not result in any reduction in the excretion of the indoleic acids. The results are interpreted in terms of a possible congenital defect in the normal conversion of tryptophan to kynurenine.

Adult↗

A sensitive assay method of furosemide in plasma and urine by high-performance liquid chromotography.

A sensitive assay method of furosemide in plasma and urine by high-performance liquid chromatography (HPLC) is described. The minimum measurable concentrations of furosemide in plasma and urine were 0.2 and 5.0 microgram/ml, respectively; whereas the coefficients of variation of furosemide levels were found to be 7.8% for plasma and 2.0% for urine. These are within the acceptably low limits. Hence, the present method of furosemide is sensitive, reproducible, and accurate for therapeutic drug monitoring. The significance of this HPLC assay method is discussed.

Chromatography, High Pressure Liquid↗

Potassium conservation with amiloride/hydrochlorothiazide ("Moduret') in thiazide-induced hypokalaemia in hypertension.

A double-blind study was carried out in 24 hypertensive patients with thiazide-induced hypokalaemia (serum potassium less than 3.2 mmol/l) to compare the effects of treatment with an amiloride/hydrochlorothiazide combination or hydrochlorothiazide alone. The study was divided into three phases: (i) potassium repletion (Weeks 0 to 4) with oral potassium chloride (40 mmol/day), (ii) stabilization (Weeks 4 to 6) of normokalaemia, and (iii) active drug treatment (Weeks 6 to 14), patients being allocated at random to receive one or other of the two treatments. Dosage was 2 tablets per day of the 5 mg amiloride plus 50 mg hydrochlorothiazide combination or of 50 mg hydrochlorothiazide alone. The results showed that blood pressure control was comparable in both treatment groups but hydrochlorothiazide alone caused a statistically significant reduction in serum potassium levels compared to the drug combination. Apart from 1 patient who developed hypokalaemia on hydrochlorothiazide alone, no other side-effects of treatment were reported.

Amiloride↗

A chylous mesenteric cyst and a study of its contents.

A case of a patient with a large chylous cyst in the mesentery of the small intestine is presented. After excision of the cyst, the chyle was analyzed with special reference to its protein and lipid content. The composition of the chyle compared with that of intestinal lymph of experimental animals suggests that the fluid in the cyst has undergone concentration in terms of protein.

Adult↗

Determination of bupivacaine in human fetal and neonatal blood samples by quantitative single ion monitoring.

The blood levels of bupivacaine administered epidurally during labour have been determined in mother, fetus and the newborn infant by quantitative single ion monitoring, following gas chromatographic separation. Concentrations were determined from the height of the peak obtained at m/e 140 derived from bupivacaine compared with that at m/e 154 derived from the internal standard, 1-n-pentyl-2-(2',6'-xylylcarbamoyl)piperidine. Results from six mothers and their infants showed that the drug passed rapidly from the maternal circulation to the infant. The plasma half-life of the drug in the newborn infant was 18 h compared with 1.25 h for the adult.

Bupivacaine↗

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.

Child↗

Measurement of prostaglandin F2alpha in human cerebrospinal fluid by single ion monitoring.

An imporved method is described for measuring low levels of prostaglandin F2alpha in small volumes of cerebrospinal fluid. Single ion monitoring of the ion at m/e 423, derived from the methyl ester tri-TMS ether derivatives of prostaglandin F2alpha and the internal standard, w-trinor-16-cyclohexyl prostaglandin F2alpha, is employed. Injection of 2 pg of prostaglandin F2 alpha derivative gave a standard deviation of +/- 9%. The majority of patients had cerebrospinal fluid levels of up to 2 ng ml-1 of prostaglandin F2 alpha, whereas in certain neurological conditions with progressive disease, elevated levels were encountered, some of which were higher than 10 ng ml-1.

Chromatography, Gas↗