Drugs chloroformate

Apart from being intermediates for organic carbonate synthesis, chloroformates are also intermediates for a variety of other commercially important materials, including pesticides, dyes, perfumes, polymers and drugs. Chloroformates, such as Me3C0C(0)CI, PhCHjOC(0)Cl and 1-(9-fluorenyl)methyl chloroformate, (4.7), are used for the protection of amino and... 

Narcosis Narcosis is a state of deep stupor or unconsciousness, produced by a chemical substance, such as a drug or anesthesia. Inhalation of certain chemicals can lead to narcosis. For example, diethyl ether and chloroform, two common organic solvents, were among the first examples of anesthesia known. Many other chemicals that you would not suspect can also cause narcosis. For example, even though nitrogen gas comprises 80% of the air we breathe and is considered chemically inert (unreactive) it can cause narcosis under certain conditions. Always work with adequate inhalation and avoid inhaling chemical fumes, mists, dusts etc. whenever possible. Use fume hoods and respirators as necessary. 

From Lobelia inflata L. by extraction of the slightly acidic extract of the drug with chloroform and subsequent purification. 

A CRO may also allow for the in-house introduction of specialized lipophilic scales by transferring routine measurements. While the octanol-water scale is widely applied, it may be advantageous to utilize alternative scales for specific QSAR models. Solvent systems such as alkane or chloroform and biomimetic stationary phases on HPLC columns have both been advocated. Seydel [65] recently reviewed the suitabihty of various systems to describe partitioning into membranes. Through several examples, he concludes that drug-membrane interaction as it relates to transport, distribution and efficacy cannot be well characterized by partition coefficients in bulk solvents alone, including octanol. However, octanol-water partition coefficients will persist in valuable databases and decades of QSAR studies. 

The most critical decision to be made is the choice of the best solvent to facilitate extraction of the drug residue while minimizing interference. A review of available solubility, logP, and pK /pKb data for the marker residue can become an important first step in the selection of the best extraction solvents to try. A selected list of solvents from the literature methods include individual solvents (n-hexane, " dichloromethane, ethyl acetate, acetone, acetonitrile, methanol, and water ) mixtures of solvents (dichloromethane-methanol-acetic acid, isooctane-ethyl acetate, methanol-water, and acetonitrile-water ), and aqueous buffer solutions (phosphate and sodium sulfate ). Hexane is a very nonpolar solvent and could be chosen as an extraction solvent if the analyte is also very nonpolar. For example, Serrano et al used n-hexane to extract the very nonpolar polychlorinated biphenyls (PCBs) from fat, liver, and kidney of whale. One advantage of using n-hexane as an extraction solvent for fat tissue is that the fat itself will be completely dissolved, but this will necessitate an additional cleanup step to remove the substantial fat matrix. The choice of chlorinated hydrocarbons such as methylene chloride, chloroform, and carbon tetrachloride should be avoided owing to safety and environmental concerns with these solvents. Diethyl ether and ethyl acetate are other relatively nonpolar solvents that are appropriate for extraction of nonpolar analytes. Diethyl ether or ethyl acetate may also be combined with hexane (or other hydrocarbon solvent) to create an extraction solvent that has a polarity intermediate between the two solvents. For example, Gerhardt et a/. used a combination of isooctane and ethyl acetate for the extraction of several ionophores from various animal tissues. 

Szabolcs determined the active principle in preparations based on miconazole and clotrimazole [15]. The two drugs were determined in ointments by extraction with chloroform, evaporation of the solvent, dissolution of the residue in acetic acid, and titration with 0.1 N perchloric acid in the presence of Gentian Violet. 

Cavrini et al. [32] reported the development of a colorimetric method for the determination of miconazole nitrate in pharmaceutical preparation. The method is based on the formation of a yellow complex between the drug and bromocresol green. The absorption peak of this complex, extracted by chloroform over the pH 2—4 range, was at 424 nm, and linear response was obtained from 3—13 pg/mL. The molar absorptivity of the complex in chloroform was 1.845 x 104. This procedure is suitable for the analysis of miconazole nitrate in commercial dosage forms. 

Musumarra et al. [43] identified miconazole and other drugs by principal components analysis of standardized thin-layer chromatographic data in four eluent systems. The eluents, ethylacetate methanol 30% ammonium hydroxide (85 10 15), cyclohexane-toluene-diethylamine (65 25 10), ethylacetate chloroform (50 50), and acetone with the plates dipped in potassium hydroxide solution, provided a two-component model that accounts for 73% of the total variance. The scores plot allowed the restriction of the range of inquiry to a few candidates. This result is of great practical significance in analytical toxicology, especially when account is taken of the cost, the time, the analytical instrumentation and the simplicity of the calculations required by the method. 

Qian et al. [46] determined miconazole nitrate and benzoic acid in paint by a thin-layer chromatographic densitometric method. The drug was spotted on a GF254 silica gel plate, developed with a 42 21 13 5 w-hexane-chloroform-methanol-... 

The stability of niclosamide was studied in simulated gastric and intestinal juices, with and without enzymes, after incubation at 37°C. The remaining intact drug and its degradation products (2-chloro-4-nitroaniline and 5-chlorosalicylic acid) were extracted with chloroform/methanol (5 1) and determined by TLC and HPLC. The drug was stable in these media for at least 6 h [68]. 

Abdel-Salam et al. [21] described a sensitive and simple spectrophotometric method for the determination of primaquine and other antimalarial drugs. The method is based on the formation of complexes between iodine (as an acceptor) and the basic drug in chloroform solution. Optimum conditions were established for the determination of primaquine, in pure form or in pharmaceutical preparation. Results were accurate and precise. 

Zheng and Sun [67] used a thin-layer chromatographic method for the analysis of primaquine and other quinoline derivatives. The drug and other compounds were chromatographed on silica gel GF254 plate, with methanol aqueous 25 28% ammonia (200 3) and chloroform dichloromethane diethylamine (4 3 1), as mobile phases. Spots were located under ultraviolet radiation. The detection limit was 12 pg/mL. Total separation could be achieved by the use of two plates and the respective mobile phase. 

Since arylazoamidoximes release nitric oxide when incubated in rat liver microso-mial fraction [172], 3-arylazo-l,2,4-oxadiazol-5-ones 136 have been prepared from the corresponding arylazoamidoximes 134 as their potential pro-drugs [172]. Reaction with chloroformate afforded compounds 135 which underwent cyclisation to 136 in alkaline medium (Scheme 6.26). 

Pohl, L.R., Branchflower, R.V., Highet, R.J., et al. 1981. The formation of diglutathionyl dithiocarbonate as a metabolite of chloroform, bromotrichloromethane, and carbon tetrachloride. Drug. Metab. Dispos. 9 334—338. 

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