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Biomedical subjects

A G Davidson

Publications and source records attributed to A G Davidson.

At least 55 records · Page 3Linked to original sources

The temperature dependence of derivative ultraviolet absorption spectra.

The effects of variation of temperature in the range 0 degrees -40 degrees C on the zero and second derivative ultraviolet absorption spectra of ten compounds have been investigated. When the temperature of the solutions was increased, most of the substances showed a linear reduction of maximum absorbance (A(max)), with temperature coefficients of -0.07 +/- 0.03% per degree. The second derivative amplitudes of all the substances were reduced, with temperature coefficients (-0.1 to -0.5% per degree) that bore no significant relationship to those of the corresponding A(max) values. These effects on the extrema of the derivative spectra are explained by the small reduction in curvature at the corresponding wavelengths of the fundamental spectra, that occurs with increasing temperature. The precise and accurate assay of substances by derivative UV spectrophotometry requires that the temperatures of the standard and sample solutions are identical at the time of measurement.

Journal Article↗

Assay of chlordiazepoxide and demoxepam in chlordiazepoxide formulations by difference spectrophotometry.

Rapid difference spectrophotometric methods for chlordiazepoxide and demoxepam in chlordiazepoxide formulations are described which overcome the nonspecificity of the official spectrophotometric assays. The procedures are based on the measurement of the difference absorbance at 269 nm of equimolar solutions of chlordiazepoxide at pH 8 and pH 3 and the difference absorbance at 263 nm of equimolar solutions of demoxepam at pH 13 and pH 8. The methods are specific for chlordiazepoxide and demoxepam in the presence of both compounds, 2-amino-5-chlorobenzophenone, certain coformulated drugs, and formulation excipients. Analyses of commercial dosage forms of chlordiazepoxide have shown the presence of demoxepam at concentrations in excess of the pharmacopoeial specifications in some aged samples.

Anti-Anxiety Agents↗

Assay of benzenoid drugs in tablet and capsule formulations by second-derivative ultraviolet spectrophotometry.

Rapid second-derivative assay procedures are described for tablet and capsule formulations of benzenoid drugs, which eliminate the interference of the formulation excipients in simple UV spectrophotometric methods. Accuracy, precision, and selectivity of the technique are discussed. The general application of the procedures for the batch assay of tablet and capsule dosage forms containing greater than or equal to 2 mg of a benzenoid drug is indicated by the results obtained for 18 such formulations, in good agreement with pharmacopeial assay results and/or declared amounts. The procedures are sufficiently sensitive to permit unit dose assays of these formulations.

Benzene Derivatives↗

Difference spectrophotometric assay of 1,2-diphenolic drugs in pharmaceutical formulations II: Germanium dioxide reagent.

A rapid, difference UV spectrophotometric assay of formulated drugs containing a 1,2-diphenolic group is described. In this assay are utilized the bathochromic shift of the absorption band of 1,2-diphenolic substances from approximately 280 to approximately 287 nm and the concomitant hyperchromic effect induced by the addition of germanium dioxide to an aqueous solution of the drug buffered at pH 6. The absorbance of the solution of the complexed drug relative to that of an equimolar solution of the free drug, which is maximum at approximately 292 nm, is proportional to the concentration of the drug and is unaffected by the presence of other UV-absorbing substances in the formulations that lack the 1,2-diphenolic moiety. Applications of the assay are described for formulations containing epinephrine, isoetharine, isoproterenol, levodopa, and methyldopa.

Catechols↗

The simultaneous assay of emetine and cephaeline in ipecacuanha and its preparations by spectrofluorimetry.

A rapid assay is described for the simultaneous determination of emetine and cephaeline in ipecacuanha and its preparations, based upon the different fluorescence intensities of the alkaloids at pH 1 and pH 12. The assay involves the measurement of fluorescence at 317 nm of dilutions of the sample in 0.1 M hydrochloric acid (pH 1) and 0.01 M sodium hydroxide (pH 12) with an excitation wavelength of 283 nm. Concentrations of the individual alkaloids are calculated using two simultaneous equations derived from the experimentally determined coefficients of fluorescence of solutions (1 mug/ml) of emetine and cephaeline at pH 1 and pH 12. The procedure, which has been shown to be accurate, precise and sensitive, requires only 1 ml of a liquid sample and less than 0.5 g of powdered root. There was reasonable agreement between the total concentrations of alkaloids in tinctures and liquid extracts of ipecacuanha determined by the spectrofluorimetric method and by the titrimetric procedure of the British Pharmacopoeia. The fluorimetric procedure gave higher levels of alkaloids in the powdered root than did the B.P. method; this difference is explained by incomplete extraction of the alkaloids in the B.P. procedure for powdered ipecacuanha root.

Journal Article↗

Difference spectrophotometric assay of 1,2-diphenolic drugs in pharmaceutical formulations - I. Boric acid reagent.

A new procedure is described for the selective determination of drugs containing a 1,2-diphenolic moiety. The assay is based upon the measurement of difference absorbance between two equimolar solutions of the drug in pH 7 phosphate buffer, one of which also contains 0.1 M boric acid. The difference absorbance, which is maximum at about 292 nm, is due to the different spectral characteristics of the boric acid ester of the drug and of the unesterified drug and is proportional to the concentration of the drug. The accuracy, precision, sensitivity and specificity of the procedure are discussed. Applications of the assay are described for adrenaline, isoetharine, isoprenaline, levodopa and methyldopa in pharmaceutical formulations.

Journal Article↗

Immunoreactive trypsin in cystic fibrosis.

Since the first observation in 1979 that CF infants have elevated blood IRT, studies in various centres have enabled us to more fully understand the importance of this phenomenon. There is increasing evidence to show that mass newborn screening for CF using the IRT assay is practical and is capable of detecting essentially all CF newborns at a cost comparable to existing screening programs for other disorders such as Hypothyroidism. Although the elevated IRT levels seen in infancy in CF soon decrease, IRT levels in older CF patients appear to quite closely reflect the capability of that patient to secrete pancreatic enzymes and can be helpful in separating CF patients whose ability to secrete enzymes is preserved, from those with diminished exocrine pancreatic function. In all CF patients there appears to be an altered relationship between pancreatic exocrine secretion and circulating IRT levels as compared to control patients. This is probably one further manifestation of a secretory obstructive defect which although not uniformly severe, is common to all CF patients.

Adolescent↗

The assay of tropane derivatives in formulations by second derivative ultraviolet spectrophotometry.

The development of a second order derivative spectrophotometric assay of atropine, hyoscine and benztropine in formulations is described. The assay involves the extraction into 1,2-dichloroethane of the tetraphenylborate salt of the alkaloids precipitated from pH 6 solution by an excess of sodium tetraphenylboron and measurement of the amplitude near 273 nm to its shorter wavelength satellite in the second derivative spectrum. The second derivative amplitude gives a more precise determination of the alkaloids than absorbance. A two-point bracketing standardization of the amplitude is required owing to a small but significant intercept in the calibration data. The procedures are sufficiently sensitive and precise for the batch and unit-dose assay of tablets of atropine sulphate (0.6 mg) hyoscine hydrobromide (0.3 mg) and benztropine mesylate (2 mg), and for the assay of atropine sulphate injection (0.4 mg ml-1) and tincture of belladonna.

Atropine↗

In vitro assessment of the intra luminal phase of gliadin digestion in coeliac disease: gamma-glutamyl transpeptidase-like activity in saliva.

gamma-Glutamyl transpeptidase (GGTP) is an enzyme of potential relevance to the digestion of dietary gliadin, and hence of possible importance in the development of coeliac disease (CD). We have confirmed that human saliva has GGTP-like activity. Comparison of this activity between treated CD patients in long-term remission, age- and sex-matched normal control subjects, and unaffected relatives of CD patients did not show statistically significant differences. Although our results have not demonstrated a primary abnormality of this particular enzyme activity in CD, the intraluminal phase of gliadin processing is potentially important in the aetiology and pathogenesis of CD and thus deserves further study.

Adult↗

Argininosuccinic aciduria. A developmental and biochemical case study.

An infant with argininosuccinic aciduria was detected through the routine newborn screening program for inborn metabolic diseases and has been followed for over 7 years. Treatment consisting of restricted protein intake and arginine base supplementation was initiated at the age of 8 months and was continued intermittently. She maintained normal psychomotor development to the age of 3 years and currently at the age of 7.3 years, she has measured intelligence in the borderline range. She has had mild symptoms of cerebellar ataxia. Her physical growth has been below normal. Biochemical abnormalities are described. Special metabolic investigations and the effects of treatment are discussed.

Amino Acid Metabolism, Inborn Errors↗

Protease binding by alpha 2 macroglobulin in cystic fibrosis.

The interaction of alpha 2 macroglobulin (alpha 2M) with exogenous proteases has been reported by others to be abnormal in cystic fibrosis (CF). We have re-examined these claims. Four parameters were considered:(1) the molar protease binding of alpha 2M; (2) the interaction of bovine cationic trypsin (BCT), complexed to alpha 2M, with low molecular mass substrate, benzoyl arginine ethyl ester (BAEE); (3) the stability of formed alpha 2 M-BCT complexes; and (4) the subunit structure of alpha 2M. We have found CF alpha 2M to be similar to control alpha 2M in every respect studied.

Adolescent↗

Secretin pancreozymin stimulation test and confirmation of the diagnosis of cystic fibrosis.

We have studied the secretin-pancreozymin stimulation test of pancreatic function with particular regard to its usefulness in the diagnosis of cystic fibrosis patients without gastrointestinal symptoms. We have compared the test results in 38 control individuals, 14 patients with cystic fibrosis and five other patients with problems affecting pancreatic function. Of the cystic fibrosis patients tested, six had no gastrointestinal symptoms and were shown to have normal or raised output of pancreatic enzymes measured (lipase, trypsin, chymotrypsin, and amylase). There was a positive correlation between both volume and bicarbonate measurement versus body weight in all subjects, but this relationship was clearly different in the cystic fibrosis patients compared with others regardless of the cystic fibrosis patients' ability to secrete pancreatic enzymes. Among the cystic fibrosis patients, bicarbonate concentration tended to be higher in those able to secrete a significant amount of pancreatic enzymes. However, the actual output of bicarbonate measured in all cystic fibrosis patients (range 0.001-0.037 mmol/kg/45 min post-stimulation) was below that found in all control patients (range 0.104-0.516 mmol/kg/45 min post-stimulation). Therefore the secretin-pancreozymin test of pancreatic function appears to be useful in the diagnosis of cystic fibrosis even in those patients with adequate enzyme production.

Adolescent↗

Use of a dried blood spot in immunoreactive-trypsin assay for detection of cystic fibrosis in infants.

We assayed more than 5000 blood spots dried on filter paper and approximately 1000 serum samples for immunoreactive trypsin, with commercial reagents (Behring and Sorin). The assay procedures were modified so that newborn screening is technically feasible. Both kits are satisfactory for serum assay, but the Sorin materials are better adapted for blood spot analysis. Immunoreactive trypsin in blood spots rapidly decreases with specimen age, but is stable in frozen serum. Values for premature infants do not differ significantly from those for full-term babies. Children with cystic fibrosis were readily distinguished from those without, up to at least one year of age.

Blood Specimen Collection↗