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Biomedical subjects

G F Johnson

Publications and source records attributed to G F Johnson.

At least 127 records · Page 7Linked to original sources
PubMed1976

Gas-chromatographic determination of 5-fluorocytosine in human serum.

We describe a sensitive and precise gas-chromatographic method, in which cytosine is used as the internal standard, for determination of an antifungal agent, 5-fluorocytosine, in serum. The trimethylsilyl derivative of this drug is well separated from the internal standard and from normal serum constituents. Amphotericin B does not interfere with the determination of 5-fluorocytosine. The lower limit of detection for 5-fluorocytosine is 1 mg/liter when 200 mul of serum is analyzed. Within-run precision (CV), established by analysis of 10 replicates, was 4.5% at a concentration of 19.9 mg/liter. Twenty-five serum samples were analyzed for 5-fluorocytosine by a microbiological assay and by the gas-chromatographic method. Mean value observed with the bioassay was 78.5 mg/liter and with our procedure was 69.4 mg/liter. When values for our assay were regressed against values for the bioassay, slope of the least-squares line was 0.85, intercept was 2.7 mg/liter, and r was 0.93.

Chromatography, Gas↗
PubMed1976

Gas-chromatographic method for acetaminophen (N-acetyl-p-aminophenol) based on sequential alkylation.

A gas-chromatographic procedure for acetaminophen is described in which the drug is chromatographed as the O-heptyl-N-methyl derivative. This derivative is prepared by a sequential alkylation procedure in which the phenolic hydroxyl group of the parent compound is alkylated off-column with heptyl iodide and the amide group is derivatized on-column by reaction with trimethylanilinium hydroxide. The internal standard, N-propionyl-p-aminophenol, is subjected to the same derivatization procedure. This gas-chromatographic procedure correlates well with conventional colorimetric and spectrophotometric procedures for acetaminophen and is more sensitive. Within-run precision (CV) was 2.0% at a serum concentration of 10.0 mg/liter (n = 10) and between-run precision was 4.0% over a period of eight months. This method is particularly applicable to studies of the pharmacokinetics of acetaminophen.

Acetaminophen↗
PubMed1976

Quantitative gas-chromatographic flame-ionization method for p-chlorophenoxyisobutyric acid in human serum and saliva.

We describe a gas-chromatographic method for p-chlorophenoxyisobutyric acid (I) the active metabolite of clofibrate. The drug and internal standards are separated from either serum or saliva by a double extraction procedure and converted to the corresponding butyl esters by reaction with iodobutane in a mixture of methanol and N,N-di-methylacetamide containing tetramethylammonium hydroxide. Within-run CV of this assay at a serum I concentration of 79.2 mg/liter was 2.3% and at a salivary I concentration of 2.5 mg/liter was 2.1%. Precision during four months of the serum and salivary assays at these concentrations was 4.1% and 6.2%, respectively. The mean serum concentration of I (12 h after dose) in patients receiving the drug at an average dose of 28.0 mg/kg per day was 109.6 mg/liter. Serum and salivary concentrations of I as determined by our procedure were used to calculate the unbound fraction of drug in human serum. Such measurements can be used to monitor therapy in patients with renal disease, where drug toxicity may arise from high concentrations of unbound I.

Chromatography, Gas↗
PubMed1976

Monitoring drug concentrations in a case of combined overdosage with primidone and methsuximide.

We describe a case of fatal overdosage with primidone and methsuximide. During the early phase of the patient's hospital course we found concentrations of methsuximide, N-desmethylmethsuximide, and primidone in serum that far exceeded the usual therapeutic concentrations, as determined by gas-liquid chromatography. Determination of N-desmethylmethsuximide in peritoneal fluid demonstrated concentrations comparable to those in serum. This led to the therapeutic decision to manage the patient by dialysis. Subsequently, serum samples collected during the course of hospitalization were analyzed quantitatively by gas-liquid chromatography for methsuximide, N-desmethylmethsuximide, primidone, phenobarbital, and diphenylhydantoin. Selected serum specimens were also analyzed by gas chromatography-mass spectrometry, and N-methyl-2-hydroxymethyl-2-phenylsuccinimide, a metabolite of methsuximide not previously described in human serum, was identified by analysis of its mass spectrum.

Adult↗
PubMed1975

A quantitative gas chromatographic determination of ethosuximide based on N-butylation.

A gas chromatographic procedure has been developed for the routine determination of the anticonvulsant, ethosuximide, in serum. Volatile butyl derivatives for gas chromatography were prepared by the method of R.H. Greeley (J. Chromatogr., 88 (1974) 229) using butyl iodide as the alkylating agent. This procedure yielded stable derivatives with improved chromatographic qualities over those obtained by methylation and proved superior to both on-column alkylation with tetrabutylammonium hydroxide and to silylation. The analysis requires 0.5 ml of serum and the between run precision of the assay at 40 mug/ml was 3.3%.

Butanols↗
PubMed1975

The Weissenbacher-Zweymuller syndrome of micrognathia and rhizomelic chondrodysplasia at birth with subsequent normal growth.

Two patients are reported with the clinical and roentgenographic findings of the Weissenbacher-Zweymuller syndrome. The features are neonatal micrognathia (Pierre Robin syndrome), rhizomelic chondrodysplasia with dumbbell shaped femur and humeri. The bone changes tend to regress and there is normal growth on serial studies. A third case seemed at birth to show similar roentgenographic changes but was dwarfed; serial observations revealed him to be a case of the Kniest syndrome with micrognathia as an added feature. The term "micrognathic dwarfism" suggested by Maroteaux is probably best aboided since it will inevitably include a variety of conditions, only some of which are associated with dwarfism.

Diagnosis, Differential↗
PubMed1975

Therapeutic monitoring of anticonvulsant drugs: gas-chromatographic simultaneous determination of primidone, phenylethylmalonamide, carbamazepine, and diphenylhydantoin.

We describe a sensitive and precise gas-chromatographic method in which benzylmalonate methylester monoamide is used as the internal standard for the simultaneous determination of primidone, phenylethylmalonamide, carbamazepine, and diphenylhydantoin. The trimethylsilyl derivatives of the anticonvulsants are well separated from each other and from normal serum constituents. The lower limit of detection for each drug is 0.5 mg/liter when 1 ml of serum is analyzed. Within-run precision (CV), established by analysis of 10 replicates, was as follows: primidone (5.4 mg/liter), 2.6%; phenylethylmalonamide (5.5 mg/liter), diphenylhydantoin (6.6 mg/liter), 3.8%; and carbamazepine (10.4 mg/liter), 3.2%. Fifty specimens were analyzed for primidone and 35 for diphenylhydantoin by a standard gas-chromatographic method involving on-column methylation and by the procedure we have developed. The mean value observed for primidone with the on-column alkylation procedure was 9.3 mg/liter and with our procedure was 9.6 mg/liter. When values for our assay were regressed against values for the standard method, the slope of the least-squares line was 0.936, the intercept was 1.00 mg/liter, and r was 0.939. The mean values observed for diphenylhydantoin by on-column methylation and with our procedure were both 12.6 mg/liter. When values for our assay were regressed against the standard method, the slope of the least-squares line was 0.944, the intercept was 0.3 mg/liter, and r was 0.988.

Anticonvulsants↗