Theophylline, theobromine, caffeine

Sample solutions 200 mg/4ml MeOH + 6mlCHCl3 100, 120, 140 pg/ml Methanol + water (1+lv/v) 50 mg/lOml methanol 

Sorbent Prescribed Silica gel G Used TLC srUca gel 60 F254 20 X 20 cm (Merck 1.05715) HPTLC silica gel 60 F254GLP 20 X 10 cm (Merck 1.05613) TLC alusheet RP-18 F254S 20 X 20 cm (Merck 1.05559) 

Solvent system 1-Butanol -1- chloroform -1- acetone -1- ammonia solution cone. (40 -1-30 + 30-1-10) Toluene+ 2-propanol + acetic add (16 + 2 + 1) Methanol + water (60 +40) 

The chromatographic system is very environmentally friendly, therefore recommended for schools. 

The following two examples are not quite so problematical with respect to handling of the solvents, but are critical with respect to the reproducibUity  

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Entry Template Polymer Capacity factors Theophylline Theobromine Caffeine... 

Included here are the five plant bases, i. e., heteroxanthine, theophylline, theobromine, caffeine and tetramethyltrihydroxypurine, and the purines from the animal kingdom such as, e.g., adenine, hypoxanthine, guanine, vernine (guanosine), isoguanine, xanthine and uric acid. 

The following methylatlons were observed 7-Methylxanthine + Theobromine 1-Methylxanthine -> Theophylline Theobromine - Caffeine Theophylline -> Caffeine 7-Methylxanthosine -> Theobromine Paraxanthine - Caffeine... 

AH three of these materials are apparentiy central nervous system (CNS) stimulants. It is beheved that for most individuals caffeine causes greater stimulation than does theophylline. Theobromine apparentiy causes the least stimulation. There is some evidence that caffeine acts on the cortex and reduces drowsiness and fatigue, although habituation can reduce these effects. 

The pur pose of work is to develop the technique of separ ation of purine bases (caffeine, theophylline, theobromine) and the technique of detection of purine bases in biological fluid by TLC using micellar mobile phases containing of different surfactants. 

The effect of concentration of cationic (cetylpyridinium chloride, CPC), anionic (sodium dodecylsulfate, SDS) and nonionic (Twin-80) surfactants as well as effect of pH value on the characteristics of TLC separ ation has been investigated. The best separ ation of three components has been achieved with 210 M CPC and LIO M Twin-80 solutions, at pH 7 (phosphate buffer). Individual solution of SDS didn t provide effective separation of caffeine, theophylline, theobromine, the rate of separ ation was low. The separ ation factor and rate of separ ation was increase by adding of modifiers - alcohol 1- propanol (6 % vol.) or 1-butanol (0.1 % vol.) in SDS solution. The optimal concentration of SDS is 210 M. 

Mehtylxanthines are naturally occurring drugs, including theophylline, theobromine and caffeine. Methylxanthines at relatively high doses inhibit phosphodiesterases, which results in an increase in intracellular cAMP... 

Another scheme for methylxanthine isolation involves the extraction of the dried ground plant with 10% ammonium hydroxide chloroform (1 10). A large proportion of the extraction mixture is used, relative to the sample, to ensure complete extraction of any theobromine. Caffeine and theophylline will be extracted easily under these conditions.20 After removing water from the organic layer, filtration, and solvent removal, any methylxanthines present will be in the residue together with some impurities. An approach to finally isolating these methylxanthines from this... 

Hieda et al. determined theophylline, theobromine, and caffeine in human plasma and urine by gradient capillary HPLC with frit fast atom bombardment (FAB) mass spectrometry with 7-ethyl theophylline as the internal standard.64... 

Hieda, Y., Kashimura, S., Hara, K., and Kageura, M., Highly sensitive and rapid determination of theophylline, theobromine and caffeine in human plasma and urine by high performance liquid chromatography frit fast atom bombardment spectrometry, J. Chromatogr., 667,241,1995... 

Foods derived from cocoa beans have been consumed by humans since at least 460 to 480 AD. The source of cocoa beans, the species Theobroma, contains a variety of biologically active components. These include the purine alkaloids theobromine, caffeine, and theophylline. Structurally, they are methylated xanthines and, thus, are often referred to as methylxanthines. Theobromine (3, 7-dimethylxanthine) is the predominant purine alkaloid in cocoa and chocolate. Caffeine (1, 3, 7-trimethylxanthine), the major purine alkaloid found in coffee and tea, is found in cocoa and chocolate at about one eighth the concentration of theobromine. Only trace amounts of theophylline (1, 3-dimethylxanthine) are detected in cocoa and chocolate products. 

Concentration of Theobromine, Caffeine, and Theophylline in Theobroma Beans (mg/g) ... 

Terada, H., Sakabe, Y., High performance liquid chromatographic determination of theobromine, theophylline and caffeine in food products, J. Chromat., 291, 453, 1984. 

In the case of the methylated xanthines, particularly theophylline, theobromine and caffeine, the preponderance of data on the metabolism of these compounds in man suggests that a methylated uric acid is the principal product. However, the data presented earlier proposes at best a 77 per cent accounting of the methylated xanthine administered. The question can be raised as to whether the final products observed upon electrochemical oxidation of these compounds aids these studies. Very recently studies of metabolism of caffeine have revealed that 3,6,8-trimethylallantoin is a metabolite of caffeine 48>. This methylated allantoin is, of course, a major product observed electrochemically. The mechanism developed for the electrochemical oxidation seems to nicely rationalize the observed products and electrochemical behavior. The mechanism of biological oxidation could well be very similar, although insufficient work has yet been performed to come to any definite conclusions. There is however, one major difference between the electrochemical and biological reactions which is concerned with the fact that in the former situation no demethylation occurs whereas in the latter systems considerable demethylation appears to take place. 

Tarka40 wrote an extensive review of the toxicology of cocoa and the methylxanthenes, theobromine, caffeine and theophyllin. The review involved... 

Fig. 15. Displacement of radio-labeled analyte analog binding to MI spheres under equilibrium condition. B/B0 is the ratio of the amount of radio-labeled ligand bound in the presence of the displacing ligand (analyte), B0. Displacement of [8-3H]theophylline binding to a polymer imprinted with theophylline. Displacing ligands theophylline ( ) theobromine (+) xanthine (o) caffeine (A). Reprinted with permission from Ye L, Cormack PAG, Mosbach K (1999) Anal Commun 36 35. Copyright 1999 The Royal Society of Chemistry...

Theophylline invariably contains other related substances as impurities, namely theobromine, caffeine and [1 -hy droxypropyl th co phy lline. 

Wilkinson JM, Pollard I. (1993). Accumulation of theophylline, theobromine, and paraxanthine in the fetal rat brain following a single oral dose of caffeine. Brain Res Dev Brain Res. 75(2) 193-99. Winstock AR, Trivedy CR, Warnakulasuriya KAAS, Peters TJ. (In press). A dependency syndrome related to areca nut use some medical and psychological aspects among areca nut users in the Gujarat community in the UK. Addict Biol. 

After the nucleic acid purines adenine and guanine, the next most prominent purine in our everyday lives is probably caffeine. Caffeine, in the form of beverages such as tea, coffee, and cola, is one of the most widely consumed and socially accepted natural stimulants. Closely related structurally are theobromine and theophylline. Theobromine is a major constituent of cocoa, and related chocolate products. Caffeine is also used medicinally,... 

Three of the most important methylxanthenes are theophylline, theobromine, and caffeine. Methylxanthenes exhibit a similar range of biological activity. 

Purine alkaloids Rubiaceae Cojfea arabica Caffeine Theophylline Theobromine... 

Doxapram Nikethamide Pentylenetetrazol Strychnine Picrotoxin Bicuculline Amphetamine Methamphetamine Methylphenidate Pemoline Ephedrine Phentermine Fenfluramine Phenylpropanolamine Caffeine Theophylline Theobromine... 

A variety of drugs in distinct pharmacological and chemical classes can be considered under the broad classification as stimulants. Xanthines and methylxan-thines constitute a weak class of stimulants that includes caffeine, theophylline (aminophylline),and theobromine. Caffeine is freely available in coffee, colas, and certain over-the-counter pills. A low degree of tolerance develops to some of their effects and a mild withdrawal syndrome is observed following immediate cessation of their repeated use. 

Tea Camellia sinensis Caffeine, theophylline, theobromine Adenosine (antagonist) Adenosine... 

The three methalated xanthine derivatives (methyixanthines) theophylline, theobromine, and caffeine are plant alkaloids. Theophylline is the only one of these which is widely used therapeutically. Three possible modes of action have been proposed ... 

The three important methylxanthines are theophylline, theobromine, and caffeine. Their major source is beverages (tea, cocoa, and coffee, respectively). The importance of theophylline as a therapeutic agent in the treatment of asthma has waned as the greater effectiveness of inhaled adrenoceptor agents for acute asthma and of inhaled anti-inflammatory agents for chronic asthma has been established, but theophylline s very low cost is an important advantage for economically disadvantaged patients in societies in which health care resources are limited. 

Known hypersensitivity to any component of this agent or methyixanthines (caffeine, theophylline, theobromine)... 

Xanthine derivatives are a group of chemically similar compounds that exert a variety of pharmacologic effects. Common xanthine derivatives include theophylline, caffeine, and theobromine (Fig. 26-2) these compounds are frequently found in various foods and beverages (tea, coffee, soft drinks). Theophylline and several theophylline derivatives are also administered therapeutically to produce bronchodilation in asthma and other forms of reversible airway obstruction (bronchitis, emphysema).65,79 Theophylline and caffeine are also potent CNS stimulants, and some of the more common side effects of these drugs are related to this CNS excitation (see Adverse Side Effects, later in this chapter). 

In 1982 a method has been presented to remove xanthines like theobromine, theophylline and caffeine from cacao products [1] working very similar to the procedures applied to the decaf-feination of coffee and tea. The authors intend to reduce the quantity of xanthines, but like to keep the content of valuable cacao butter unchanged. For this purpose they suggest to swell the cacao material (nibs) with water to about 40 % w/w and extract the undesired components with Carbon dioxide. They claim that the concentration of theobromine is reduced, caffeine is removed completely without affecting the cacao butter. 

The prototypical structural class of nonselective PDE inhibitors is represented by the methylxanthines (Figure 9.4), a family of plant-derived alkaloids that includes theophylline (1), caffeine (2), and theobromine (3) [9], Although limited in potency, these simple naturally occurring xanthines were the parents in the later discoveries of more potent synthetic derivatives such as pentoxyfylline (4) and isobutylmethyl-xanthine (IBMX, 5). In particular, the latter compound has been widely used and has been regarded for decades as the gold standard nonselective inhibitor of all PDEs. Only recently has it become clear that some of the newer PDEs (8 and 9) are not inhibited by IBMX. Derivatives of IBMX carrying substituents at the 8 position confer increased potency [10], An example is compound 6, which retains most of... 

Disposition in the Body. Rapidly absorbed after oral administration bioavailability almost 100%. Metabolic reactions include V-demethylation and oxidation to uric acid derivatives. About 85% of a dose is excreted in the urine in 48 hours with up to 40% of the dose as 1-methyluric acid, 10 to 15% as 1-methylxanthine and up to 35% as 5-acetylamino-6-formylamino-3-methyluracil and 5-acetylamino-6-amino-3-methyluracil other metabolites excreted in the urine include theophylline, 1,7-dimethylxanthine (paraxanthine), 7-methylxanthine, and 1,3-dimethyluric acid. Less than 10% is excreted in the urine as unchanged drug. The extent of V-acetylation is genetically determined. Caffeine, theophylline, theobromine, and paraxanthine are found in plasma from dietary sources especially coffee, tea and cocoa. An average cup of coffee or tea contains approximately 100 mg of caffeine. 

The technique of ultrafiltration for serum sample preparation has been studied by several investigators (H7, HIO, K9, S19, V4, V5). In this technique the serum sample is passed through an exclusion membrane which exhibits a 95% retention for compounds with MW > 25,000. Thus, low-molecular-weight constituents pass through the membrane, whereas proteins or protein-bound constituents are retained. Hartwick ct al. (HIO) reported excellent recoveries for xanthosine, inosine, guanosine, theobromine, theophylline, and caffeine. Tryptophan showed poor quantitative recovery in accordance with the findings of previous investigators (K33, 01). 

Figure 18-7. Effect of temperature on the separation of caffeine derivatives on a Hypercarb column (1 mm x 100mm). (a) Column at 100°C, mobile phase acetonitrile (b) Colnmn at 180°C, mobile phase water/acetonitrile 70/30. Samples 1, hypoxantine 2, theobromine 3. theophylline 4, caffeine 5, P-hydroxyethyltheophylline. (Reproduced from reference 35, with permission.)...

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