Theophylline acidity

This experiment describes the quantitative analysis of the asthma medication Quadrinal for the active ingredients theophylline, salicylic acid, phenobarbital, ephedrine HGl, and potassium iodide. Separations are carried out using a Gi8 column with a mobile phase of 19% v/v acetonitrile, 80% v/v water, and 1% acetic acid. A small amount of triethylamine (0.03% v/v) is included to ensure the elution of ephedrine HGl. A UV detector set to 254 nm is used to record the chromatogram. 

Otherwise cyanoacetic acid is directiy converted as a solution with 1,3-dimethylurea [96-31-1] iato 2-cyano-A/,AT-dimethylcarbamoyl acetamide [39615-79-7] which is further upgraded iato the diuretics theophylline [58-55-9] (33 where R = H) and caffeiae [58-08-2] (33, where R = CH3) (63). 

A derivative of an isomeric azapurine ring system interestingly exhibits bronchodilator activity, possibly indicating interaction with a target for theophylline. The starting pyridazine 97 is available from dichloro compound 96 by sequential replacement of the halogens. Treatment of 97 with formic acid supplies the missing carbon and cyclizes the intermediate formamide with consequent formation of zindotrine (98) [16]. 

The melting point of the pure nicotinic acid salt is 180°C and the yield is 75% to 80% related to the used theophylline. The substance has a nearly neutral reaction and is very readily soluble in water. 

Choline theophyllinate Choline chloride Carbachol Choline salicylate Choline dihydrogen citrate Ferrocholinate Chromic acid... 

Several selective interactions by MIP membrane systems have been reported. For example, an L-phenylalanine imprinted membrane prepared by in-situ crosslinking polymerization showed different fluxes for various amino acids [44]. Yoshikawa et al. [51] have prepared molecular imprinted membranes from a membrane material which bears a tetrapeptide residue (DIDE resin (7)), using the dry phase inversion procedure. It was found that a membrane which contains an oligopeptide residue from an L-amino acid and is imprinted with an L-amino acid derivative, recognizes the L-isomer in preference to the corresponding D-isomer, and vice versa. Exceptional difference in sorption selectivity between theophylline and caffeine was observed for poly(acrylonitrile-co-acrylic acid) blend membranes prepared by the wet phase inversion technique [53]. 

Kinoshita, Imoto etal.11 14) synthesized other anionic models, 5 (APVP), CPVP, UPVP, TPVA, HPVA, THPVA, and 6 (AMPPVA), by the polymer reaction of N-eoupled(2-dihydrogenphosphate)-ethylderivatives of nucleic acid bases (or adenosine-5 -phosphate, AMP) with polyvinylaleohol. A, C, U, T, H, and TH denote adenine, cytosine, uracil, thymin, hypoxanthine, and theophylline, respectively. The authors reported the apparent hypochromities of 3 to 16% for many kinds of mixtures of the models and DNA or RNA, as compiled in Table 1. However, for the mixtures APVA + RNA, HPVA + RNA HPVA + DNA, THPVA + RNA, CPVA + DNA and CPVA + RNA, no hypochromicity was detected. 

Nucleic acids are anionic under the neutral conditions. Thus, the syntheses of model compounds of the opposite charge are interesting for the discussion of electrostatic contributions in specific interactions of nucleic acids. We have tried to synthesize cationic models by the Menschutkin reaction of poly-4-vinylpyridine with 9-(2-chlo-roethyl)adenine, l-(2-chloroethyl)thymine, and 7-(2-chloroethyl)theophylline15,16 The obtained polymers are poly l-[2-(adenin-9-yl)ethyl]-4-pyridinioethylene chloride 7(APVP), poly l-[2-(thymin-l-yl)ethyl]-4-pyridinioethylene chloride 8 (TPVP), and poly l-[2-(theophyllin-7-yl)ethyl]-4-pyridiniothylene chloride 9 (THPVP), respectively. 

A hypochromicity was observed between THPVP and APVP (or TPVP). Since theophylline is not a nucleic acid base and does not form hydrogen-bonding, these observations indicate that stacking-type hydrophobic forces are important. 

C5H7NO2 105-56-6) see Allopurinol Amlexanox Bemegride Ethosuximide Etozolin Folic acid Gabapentin Paroxetine Phensuximide Sulfadimethoxine Theophylline Tinoridinc Trimethoprim Valdetamide Valproic acid ethyl 2-(2 -cyanobiphenyl-4-ylmethylamino)-3-nitroben-zoate... 

Care must be exercised in the choice of acid employed in chloramine T — mineral acid reagent since the detection sensitivity and also the color of the fluorescences produced depend to a significant extent on the choice of acid. This is illustrated for the purine derivatives caffeine, theobromine and theophylline in Figure 1 and Table 1. 

Fig. 1 Comparison of the detection sensitivity after derivatization of three purine derivatives with chloramine T - sulfuric acid (A) and chloramine T - hydrochloric acid (B). Measurement X. (. = 365 nm, A.(, = 440 nm (monochromatic filter M 440) 1 = theophylline, 2 = theobromine, 3 = caffeine.

Figure 5. Chromatograms for theophylline in plasma extracts. Arrow indicates tneophyUine peak. Conditions 50 cm X 3 mm (i.d.) column with 10 fjm silica gel (Micropak Si 10 Varian) mobile phase, 84/15/1 chloroform/isopropanol/acetic acid flow rate, 40 rm/hr detector, UV,273nm(40).

Much research has centered on identifying the source of the purine ring in caffeine. Two possible sources are likely methylated nucleotides in the nucleotide pool and methylated nucleotides in nucleic acids. Extensive experimental work by Suzuki and Takahashi27-30 proposes a scheme whereby caffeine is synthesized from methylated purines in the nucleotide pool via 7-methylxanthosine and theobromine. Information relating to the formation of 7-methylxanthine from nucleotides in the nucleotide pool is sparse. They also provide data that demonstrate that theophylline is synthesized from 1-methyladenylic acid through 1-methylxanthine as postulated by Ogutuga and Northcote.31... 

HPLC allows a quantitative determination with relatively simple extractions. In many cases, extraction only involves a heating of the commodity with water, followed by filtration and injection onto an HPLC column. In the determination of caffeine, theobromine, and theophylline in cocoa, coffee, or tea, as well as in other foods, there is scarcely a month that passes without a new paper on this assay. Kreiser and Martin provide typical conditions for analysis.28 In their studies, samples were extracted in boiling water and filtered prior to injection onto the HPLC column. The HPLC conditions used a Bondapak reversed phase column and a mobile phase of water methanol acetic acid (74 25 1) with detection at 280 nm. This method is accurate, precise, and conserves time. It has also been adopted by the AOAC as an official method for the determination of theobromine and caffeine in cocoa beans and chocolate products.29... 

The key metabolites of caffeine (a trimethylxanthine) found in plasma, are the dimethylxanthines paraxanthine, theophylline, and theobromine the monomethylxanthine 1-methylxanthine the C-8 oxidized monomethylxanthine 1-methyluric acid and the ring oxidized uracil 5-acetyl-amino-6-amino-3-methyluracil. 

Liver metabolism is affected by methylxanthines. In high doses, theophylline and caffeine increase the level of cyclic AMP. Very high levels of methylxanthines decrease the level of branched chain and aromatic amino acids in plasma. Coffee appears to have little effect on ethanol metabolism. 

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