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In this paper, the operational 3D variational data assimilation system (3D‐var) of the Canadian Meteorological Centre (CMC) is described and its performance is compared to that of the previously operational statistical interpolation analysis. Deliberately configuring the 3D‐var to be as close as possible to the statistical interpolation system permits an evaluation of the impact of data selection on both the analysis and the resulting forecasts. The current implementation of the 3D‐var is incremental in the horizontal and the vertical since the analysis increments are constructed at a lower horizontal resolution on prescribed pressure levels. They are subsequently interpolated vertically to the σ levels of the model. The results show that although there could be significant differences in the single analysis increments, the impact on the resulting forecasts is neutral. The 3D‐var implements a multivariate covariance model implicitly through changes of variables. It is shown that the implicit cova...

For the development of radioimmunoassay procedures for tricyclic antidepressants, two drug haptens were synthesized for each of the two amitriptyline-nortriptyline and imipramine-desipramine groups. In one case, nortriptyline or desipramine was treated with succinic anhydride to yield N -(3-carboxypropionyl) derivatives; in the other case, the haptens were novel, N -(2-carboxyethyl) derivatives. The hapten and its corresponding ester were characterized by GLC-mass spectrometry, PMR spectrometry, and IR spectrophotometry. Each hapten was coupled to bovine serum albumin, and the number of hapten residues per mole of bovine serum albumin was determined by UV spectrophotometric methods. Antibodies to each hapten protein conjugate were developed in rabbits, and titers of the antiserums were checked by evaluating their binding characteristics to tritiated drug.

Sensitive specific methods are described for the determination of phenylbutazone and its metabolite oxyphenbutazone from the same plasma sample. The sample, to which an internal standard 5-(4-hydroxyphenyl)-5-phenylhydantoin (Standard II) is added, is first extracted with ether to remove interfering substances and then with n-heptane under acidic conditions to separate phenylbutazone, which is determined on a gas chromatograph by flash methylation (310°) with trimethylanilinium hydroxide using 1-(o-chlorophenyl)-1-(p-chlorophenyl)-2,2,2-trichloroethane as the external standard (Standard I). The aqueous acidic residue from which the phenylbutazone has been selectively removed is shaken again with ether to extract the oxyphenbutazone, which is analyzed with a different GLC system with flash methylation (310°) against Standard II. The methods are of sufficient sensitivity to determine plasma levels in humans after a 200-mg dose of phenylbutazone (phenylbutazone, 1 μg/ml; oxyphenbutazone, 0.5 μ/gml).

A method for the quantitative estimation of quinidine in biological fluids is described. Plasma containing quinidine, to which a known amount of cinchonidine is added as the internal standard, is extracted at pH 12.0 with benzene. The residue from the extract is mixed with 25 μl of trimethylanilinium hydroxide in methanol, and aliquots (1–2 μl) are injected into a gas chromatograph in which the injection port is held at 350°. The methyl derivatives of quinidine and the internal standard give well-separated symmetrical peaks. Detection by flame ionization gives a linear response over the range of 0.2–12.0 μg quinidine/ml plasma. The limit of detectability is 0.05 μg/ml and the method is adequate for following blood profiles of 200-mg quinidine sulfate doses in humans.

A GLC procedure was developed for the quantitative estimation of intact chlorpropamide and tolbutamide concentrations in plasma; the drugs are used as mutual internal standards. After extraction of plasma containing the drug and internal standard with toluene, the dried residue is treated with ethereal diazomethane to form the methyl derivatives of tolbutamide and chlorpropamide. Aliquots of the ethereal solution are injected into a gas chromatograph equipped with a glass‐lined injection port and glass column packed with a phenyl methyl silicone fluid (OV‐25) on Chromosorb W, which facilitates the intact determination of the methyl derivatives of the drugs. The response to the flame‐ionization detector was linear over a range of 0.20–25 μg/ml, with a 0.05–μg/ml limit of detectability for both drugs. The method compares favorably with a recently developed high‐pressure liquid chromatographic procedure and is adequate for following blood level profiles of single doses of chlorpropamide (125 mg) and tolbutamide (250 mg). Mass spectral evidence showing that intact sulfonylureas are measured is presented.