Trimethylanilinium hydroxide deriv

A brief comment should be made concerning the technique of "on-column" methylation. This is a technique wherein a methylating agent is injected along with the drug into the gas chromatograph whose temperatures initiate and complete derivatization. Trimethylanilinium hydroxide is the most commonly employed reagent and has been used to form the 1,3-dimethyl derivatives of barbiturates which do not form stable TMS derivatives (29). 

Skinner et al. (55) used GC/MS in their analyses of barbiturates. Samples were methylated (1,3-dimethyl derivatives) on-column using trimethylanilinium hydroxide. The analysis was conducted on 3% OV-1 on Gas Chrom Q. Temperature was programmed from 120 to 220°C at 10°C/min. 

L Ogierman. Analysis of phenylurea herbicides by formation of methylated derivatives in the gas-liquid chromatograph using trimethylanilinium hydroxide. Fresenius Z Anal Chem 320 365-368, 1985. 

Methylation of the phenolic OH in the product of Emde degradation decinine (32) with trimethylanilinium hydroxide (24) resulted in cleavage the lactone ring to yield derivative 33. 

Our original method for A9-THC explored this problem to some extent. Rather than attempt the synthesis of deutero labeled A9-THC we decided to analyze A9-THC as its own methyl ether (Fig. 2). Our internal standard would be l-0-perdeuteriomethyl-A9-THC. It was proposed to convert A9-THC to its 1-0-methyl ether for the analysis. This was effected by the co-injection of trimethylanilinium hydroxide and A9-THC. At the elevated temperatures of the injector port the phenol is converted to its methyl derivative. This conversion is both reproducible and quantitative. It is therefore suitable for use in any analytical technique. ... 

The problem of lipophiles remained and here again we could make use of the acid functionality of the phenols. With less lipid soluble phenols such as the steroids, simple back extraction from organic solvent into strong base would have been sufficient. However, the high lipid solubility of A9-THC necessitated that extraction be carried out with Brodie s solvent (hexane and isoamyl alcohol) and that back extraction be done with Claisen s alkali, which is a mixture of KOH, methanol, and water. After acidification of the Claisen s alkali, A9-THC could be recovered by extraction. The external standard and the trimethylanilinium hydroxide were added and the extracted phenol (i.e. A9-THC) was converted to the 1-0-methyl derivative in the injector port and the determination carried out... 

The thermal decomposition of tetramethylammonium salts of barbiturates is a procedure used extensively for their methylation [512-515]. Decomposition is performed at 240°C (temperature of the injection port) with analysis on SE-30, QF-1 and similar stationary phases. The use of trimethylanilinium hydroxide leads to better reproducibility of the preparation of the phenobarbital derivatives and to an improvement in the quantitative results [516,517]. The disadvantage of this procedure is the dependence of the course of the reaction on several parameters, e.g., geometry of the injection port, temperature. 

Gas Chromatography. This can be used to detect these compounds using 3% SE-30 on 80-100 mesh Chromosorb G (System GD, p. 194). The compounds should be converted to their methyl derivatives by heating the Acid Fraction obtained from the solvent extraction of horse urine (see above) in a sealed tube at 100 for 30 minutes with 180 il of iodomethane and 50 mg of potassium carbonate. Trimethylanilinium hydroxide is not recommended for methylating these compounds. 

Midha and Charette carried out quantitative determinations of quinidine in plasma and whole blood. Cinchonidine was added to the plasma sample to be analyzed as an internal standard. The alkaloids were extracted with benzene at pH 12.0. The residue from the extract was mixed with 25 yl of trimethylanilinium hydroxide in methanol, and aliquots (1-2 ul) were injected into the gas chromatograph in which the injection port was held at 350°C. The methyl derivatives of quinidine and the internal standard gave well separated symmetrical peaks. Detection by flame ionization gave a linear response over the range 0.2-12.0 vg quinidine/ml plasma. The limit of detectability was 0.05 ug/ml and the method was adequate for following blood profiles of 200 mg quinidine sulphate doses in humans. The recovery of quinidine... 

Various acyl derivatives (31)-(35) of schumannificine (28) detailed in Table 6 have been prepared by standard methods using the appropriate acyl anhydride or chloride [41,43]. Schumannificine has also been methylated at C-7 and C-5 by treatment with trimethylanilinium hydroxide in methanol to yield (36),(37) [43]. 

The method (27) describes the measurement of clonidine in human plasma and urine by combined gas chromatography-mass spectrometry with ammonia chemical ionization. Addition of [ 84] clonidine to plasma or urine is followed by ethylacetate extraction of clonidine from alkaline medium, back extraction into acid extraction into ethyl ether from alkaline medium and evaporation of the extract to dryness. Trimethylanilinium hydroxide is added to the residue, and dimethyl derivatives of clonidine are formed by on column methylation with an injection-port temperature of 250 for g.c. -70-eV m.s., the glass column (1.8 m X 2 mm) packed with 3% of OV-17 on Gas-Chrom Q (100 to 120 mesh) is operated at 245 . With He s carrier gas (15 ml min" ) NH3 is admitted to an ion-source pressure of 0.2 Torr, and ions are monitored at m/e 258 and 264. Graphs of peak height ratios (m/e 258 to 264) vs amounts of clonidine in urine (up to 40 ng ml-i) and in plasma (up to 5 ng ml i) are rectilinear. The precision for assay of clonidine in plasma is 11% at 0.25 ng ml" and 5% at 0.5 ng ml" and the lower limit of determination is 0.1 ng ml. ... 

More recently, the reagent of choice for the pyrolytic methylation reactions has been trimethylanilinium hydroxide, because the N,N-dimethylaniline is a better leaving group and thus a lower inlet temperature may be used [126-130]. An even better leaving group is obtained with the m-trifluoromethyl derivative of TMAH, TMTFTH [130]. 

N-Acetylacetonyl methyl ester derivatives were prepared as described by Schier et aj. (8) by dissolving the peptide in a methanolic solution of trimethylanilinium hydroxide and adding acetylacetone. After a 3 hour reaction period, the mixture was evaporated under nitrogen and the sample inserted into the mass spectrometer using a direct insertion probe. The probe was heated until ions appeared at m/e 122 for protonated dimethylaniline indicating methylation of the peptide and then spectra were recorded. 

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