Dobutamine hydrochloride

Figure 7 The effect of chamber pressure on the rate of primary drying, (a) 0.18 M methylprednisolone sodium succinate 2 mL in molded vials (2.54 cm2), shelf temperature +45°C. (Smoothed data from Ref. 6.) (b) Dobutamine hydrochloride and mannitol (4% w/w in water), 12 mL in tubing vials (5.7 cm2) and shelf surface temperature +10°C. (MJ Pikal. Unpublished data.) (Modified from Ref. 1.)... 

A DTA thermogram of dobutamine hydrochloride, at a heating rate of 5°C per min. in a nitrogen atmosphere of 40 cc per min., shows (figure 1) an endotherm at 196°C which appears to indicate a melt. 

A TGA thermogram of dobutamine hydrochloride, run simultaneously with the DTA, shows (figure 1) no weight loss until 233°C which results from decomposition. 

Dobutamine hydrochloride generally crystallizes in a random manner usually from an oil (1). This results in a nondescript crystalline formation. In only few cases does the drug exhibit any crystalline habit of interest. Upon careful and patient crystallization small thin plates and/ or small needles are formed. 

The following data describe the pattern for dobutamine hydrochloride, where d is equal to the interplanar spacing measured in terms of Angstroms (A). The ratio I/It is the intensity of the X-ray maxima based upon a value of 100 for the strongest line. A b indicates a broad line resulting from failure to resolve two closely spaced diffraction maxima. 

Thermograviraetric Analysis and Differential Thermal Analysis Thermograms of Dobutamine Hydrochloride... 

The spectrum exhibits maxima at 281 and 223 nm with molar absorptivities of 4,768 and 14,400, respectively. When aqueous potassium hydroxide is added to the methanolic solution of dobutamine hydrochloride the maxima at 281 and 223 shift to 293 (e=6,100) and 240 nm, respectively. These shifts are reversible by addition of hydrochloric acid. When the absorption spectrum of the drug is recorded in water rather than methanol, slight shifts in peak positions and intensities are observed ... 

The infrared spectrum of dobutamine hydrochloride in a potassium bromide disk is given in figure 3. Major band assignments are as follows ... 

The mass spectrum of dobutamine hydrochloride given in figure 5 shows the molecular ion of the free base at m/e 301. The major fragmentation consists of a cleavage beta to the nitrogen to yield peaks at m/e 123 and 178 with relative intensities, to the base peak, of 15.2 and 97.6%, respectively. The base peak is at m/e 107. 

XIII). Compound (XIII) is added to aqueous methanol then small amounts of hydrochloric acid are added to produce dobutamine hydrochloride (XIV). 

About 5 ml of dobutamine hydrochloride solution in water, 1 mg/ml, is acidified with two drops of concentrated nitric acid. When a drop of 0.1 N silver nitrate is added to this solution a white precipitate is formed which is readily solubilized by the addition of 3 drops of ammonium hydroxide. This indicates the presence of chloride ion. 

The secondary amine function of dobutamine hydrochloride may be determined by potentiometric titration with perchloric acid using glacial acetic acid as a nonaqueous solvent. Mercuric acetate is used to tie up the chloride ion. 

A sample of dobutamine hydrochloride containing at least 2 mg of chlorine is ignited in a Schoniger flask containing 20 ml of water. Three drops of diphenyl carbazone (5 mg/ml) in methanol are added to the solution of the completely burned sample. Mercuric nitrate, 0.5 N, is then used to titrate this solution to the first sign of rose color, using a 1 ml microburette ... 

The Rf value for dobutamine hydrochloride when chromatographed on a silica gel 60 F254 thin layer plate developed by ethyl acetate/n-propanol/water/acetic acid (100/40/15/5 v/v/v/v) in an unsaturated chamber is about 0.67. The spot of the drug may be visualized under short wavelength UV light (254 nm), or under white light after exposure to iodine vapors. 

Silylated dobutamine hydrochloride (by reaction with N-triraethyIsilylimidazole) may be chromatographed on a 3 foot glass column packed with 3% OV-225 on Chromosorb G AW-DMCS (100/120 mesh). 

Dobutamine hydrochloride may be analyzed on a C18 reversed-phase column eluted with 75%... 

Plasma levels of dobutamine hydrochloride are determined by reaction of the drug with 3H-methyl-S-adenosylmethionine in the presence of catechol O-methy1-transferase. The radioactivity of the labeled methyl derivative is determined by a liquid scintillation counter using an external standard. The final recovery of added dobutamine as 3H-CH3-dobutamine is 24.9 1.3% in the range of 2 to 170 ng/ml (4). When 14C-dobutamine is administered the samples are counted by a double isotope method. 

Dobutamine hydrochloride may be determined in plasma levels, after extraction, on a C18 reversed-phase column eluted with 22% aceto-nitrile-78% 0.1 M phosphate buffer (pH 2.0) at 2 ml/minute. The drug and its metabolite are detected by a fluorescent detector with an excitation wavelength of 195 nm and a 330 nm emission cut off filter. The retention times of dobutamine and the 3-methoxy metabolite are 5.2 and 7.9 min., respectively. The lower limit of sensitivity is 10 ng/ml. Reproducibility is 5% over a 25-300 ng/ml range. Nylidrin is used as an internal standard (6). 

Diphenhydramine hydrochloride, 3,173 Diphenoxylate hydrochloride, 7,149 Disulflram, 4, 168 Dobutamine hydrochloride, 8,139 Droperidol, 7,171 Echothiophate iodide, 3,233 Epinephrine, 7, 193 Ergotamine tartrate, 6,113 Erythromycin, 8,139 Erythromycin estolate, 1, 101 2, 573 Estradiol valerate, 4,192 Ethambutol hydrochloride, 7,231 Ethynodiol diacetate, 3,253 Fenoprofen calcium, 6,161 Flucytosine, 5,115 Fludrocortisone acetate, 3, 281 Fluorouracil, 2,221 Fluoxymesterone, 7,251 Fluphenazine enanthate, 2, 245 4,523 Fluphenazine hydrochloride, 2,263 4,518 Gluthethimide,5,139 Gramicidin, 8,179 Griseofulvin, 8,219 Halcinonide, 8,251 Halothane, 1, 119 2,573 Hexetidine, 7,277 Hydralazine hydrochloride, 8,283 Hydroflumethiazide, 7,297 Hydroxyprogesterone caproate, 4,209 Hydroxyzine dihydrochloride, 7,319 Iodipamide, 3,333 Isocarboxazid, 2, 295... 

DOBUTAMINE HYDROCHLORIDE INJECTION 250MG 20ML SINGLE DOSE VIAL 6505012394660 VI 4.94 ... 

Diethylenetriamine [111-40-0] Dobutamine hydrochloride [49745-95-1] 1207D I(1)396A, N(1)266B IE1225000 USP... 

Cardiac sympathomimetics dobutamine hydrochloride dopamine hydrochloride eninephrine hydrochloride isoproterenol... 

More than 220 producers of CRMs throughout the world produce today 12,000 20,000 materials with dif ferent matrixes, analytes and properties [4]. However, many testing (analytical) laboratories cannot find suitable CRMs in the market and develop in-house reference materials (IHRMs) themselves. Often IHRMs are developed in a laboratory to conserve the corresponding expensive CRMs. For example, a pharmaceutical company Chemagis Ltd. produces 30 active pharmaceutical ingredients steroids, benzodiazepines, antihistamines, hipolipidaemics, blood flow reactants, etc. Only for a few of them Mo-metasone Furoate, Fluticasone Propionate and Dobutamine Hydrochloride are of fi-cial reference standards for assay supplied by US, British and European Pharmacopoeias with prices of about 180 per unit (50 200 mg). Thus, to support its customers Chemagis is forced to develop IHRMs for assay as well as for impurities and related substances of each produced compound. Therefore, certification of such IHRMs that leads to traceable values is very important. 

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