Characterization of Drugs

7/28/2019 Characterization of Drugs

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ASSIGNMENT TOPIC: CHARACTERIZATION OF DRUGSSUBJECT TITLE: ORGANIC PHARMACEUTICALS

COURSE NO:PHM-CHEM-7102SUBMITTED BY: SAHAR KHAN

MS/M.PHIL PHARMACEUTICAL CHEMISTRYFIRST SEMESTER

ROLL NO. 10-MSPC-12CHEMISTRY DEPARTMENT GCU, LAHORESUBMITTED TO: SIR MUHAMMAD ISLAM

DATE OF SUBMISSION: 03-01-2013LAST DATE OF SUBMISSION: 04-01-2013


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CONTENTS DEFINATIONS OF CHARACTERIZATION CHARACTERIZATION REQUIREMENT TYPES OF CHARACTERIZATION SOURCES OF INFORMATION FOR DRUG CHARACTERIZATION PHYSICAL CHARACTERIZATION CHEMICAL CHARACTERIZATION CHARACTERIZATION OF CAFFEINE ISOLATION OF CAFFEINE PHYSIOCHEMICAL PROPERTIES OF CAFFEINE METHODS OF DETERMINATION OF CAFFEINE QUALITATIVE AND QUANTITATIVEANALYSIS OF CAFFEINE


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CHARACTERIZATIONDEFINATION No. 1

Checking composition of a given compound is called characterization. "

DEFINATION No. 2

Analysis of physio chemical properties of a given compound according to WHO iscalled characterization.

DEFINATION No. 3

Just to determine the composition of all compounds including drugs is calledcharacterization.

DEFINATION No. 4

To check the structure, formula of a compound, functional group by using differentinstruments e.g UV Spectroscopy, IR Spectroscopy, Mass Spectroscopy and NMR Spectroscopy allincludes characterization.

DEFINATION No. 5

Isolation of active ingredient from start to end is called characterization e.gisolation of caffeine from tea leaves.

DEFINATION No. 6

To isolate, purify and identification of component/constituents of drug by usingThin Layer Chromatography (TLC), High Performance Liquid Chromatography (HPLC).

DEFINATION No. 7

Qualitative and quantitative tests to identify either the given plant / Drugcontain, Alkaloids, Carbohydrate, Hormones, Lipids, Protein, Starch or Tannin as active ingredient.01

DEFINATION No. 8

A group of tests to characterize drug components are also includes in characterization.

Characterization requirementDrug characterization studies can provide information useful for drug law enforcement authorities.Chemical links between samples can be established, and material from different seizures can be classifiedinto groups of related samples.02


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It has played a major role in pharmaceutical advances, forensic science and modern agriculture. Diseasesand their remedies have also been a part of human lives. Characterization plays an important role inunderstanding remedies, i.e. drugs. Medicines or drugs that we take for the treatment of variousailments are chemicals, either organic or inorganic. However, most drugs are organic molecules. Let ustake aspirin as an example. It is probably the most popular and widely used analgesic drug because of its

structural simplicity and low cost. Aspirin is chemically known as acetyl salicylic acid, an organicmolecule. The precursor of aspirin is salicin, which is found in willow tree bark. However, aspirin caneasily be synthesized from phenol using the Kolbe reaction.03

In order to have a proper understanding and knowledge of drugs and their behavior, there is no otheralternative but to characterize drugs . Every-where, from discovery to development, from productionand storage to administration, and from desired actions to adverse effects of drugs, drugcharacterization is involved directly. In the drug discovery stage, suitable sources are explored. Sourcesof drug molecules can be natural, e.g. narcotic analgesic, morphine, from Papaver somniferum (Poppyplant), synthetic, e.g. a popular analgesic and antipyretic, paracetamol, or semi-synthetic, e.g. semi-synthetic penicillins.

Types of characterization Initial Drug Substance Characterization (IDSC) Physical Characterization

Chemical Characterization Qualitative Characterization

Quantitative Characterization

Initial Drug Substance Characterization (IDSC)An Initial Drug Substance Characterization (IDSC) report contains physical characterization

and preformulation data.

Physical characterization data include form identification, solvent identification, hygroscopicity,micromeretics, and structure elucidation. Polymorph screening and form identification are also available.Preformulation data include equilibrium solubility, pH solubility, partition coefficient, pKa determination,and accelerated physical and chemical stability.

Physical Characterization x-ray powder diffraction (XRPD) optical microscopy differential scanning calorimetry (DSC) thermogravimetry (TG) melting point determination moisture sorption/desorption isotherms infrared (IR) spectroscopy Raman spectroscopy solid-state NMR spectroscopy ultraviolet (UV)spectrum


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particle size distribution surface area scanning electron microscopy

Structure Elucidation nuclear magnetic resonance (NMR) solution NMR spectroscopy sIR spectroscopy single crystal structure determination mass spectrometry

Preformulation Data equilibrium solubility pH solubility pKa determination

Log P Log D accelerated physical and chemical solid and solution stability 04

Sources of information for drug profiling and characterization:1. Whether drug characterization work is for evidential or intelligence purposes, it is advantageous toobtain as much information on a drug sample as possible. The forensic chemist, in carrying out suchcharacterization/profiling studies, largely relies on two different sources of information

Physical Analysis

Chemical Analysis

2. the most appropriate analytical approach for drug characterization studies depends on the type ofsample, i.e., tablets, capsules, powders, liquids and natural materials (e.g., opium, cannabisproducts). The most simple type of investigation is a visual inspection of the physical characteristicsof the sample. In many cases differences/similarities in, for example,the color, texture or general appearance of samples can be observed.The forensic chemist, in combining this information with information from other sources, may beable to draw conclusions on whether or not two or more drug samples are connected.

3. Valuable information to show that samples may be more directly related canalso be obtained by comparison of their packaging (including materials, the way of packaging, andthe examination of any fingerprints on packaging), and by examination of any characteristic marksthe samples may display. Different seizures of illicit tablets, for instance, may be linked to a

distribution network, a single source of production, and in some cases to the actual equipment usedfor tableting, by examination of the defects or marks on the tablet surfaces.

4. In addition to the examination of physical characteristics, and especially where these have limitedsignificance, samples can also be characterized by chemical analysis. The detailed chemical analysisof drug samples by modern analytical techniques assigns to every drug sample a characteristicchemical signature of major, minor and trace components. Careful examination of theseimpurity profiles offers a valuable means of comparing and grouping different seizures.02


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Physical properties of drug molecules:

Physical stateDrug molecules exist in various physical states, e.g.

amorphous solid

crystalline solid

hygroscopic solid liquid or gas.

The physical state of drug molecules is an important factor in the formulation and delivery of drugs.

Melting point and boiling point:The melting point (m.p.) is the temperature at which a solid becomes a liquid The boiling point(b.p.) is the temperature at which the vapour pressure of the liquid is equal to the atmosphericpressure

For example, the melting point of water at 1 atmosphere ofpressure is 0 _C (32 _F, 273.15 K; this is also known as the ice point) andthe boiling point of water is 100 _C.

Melting point is used to characterize organic compounds/drugs and toconfirm the purity. The melting point of a pure compound is alwayshigher than the melting point of that compound mixed with a smallamount of an impurity. The more impurity is present, the lower themelting point. Finally, a minimum melting point is reached. The mixingratio that results in the lowest possible melting point is known as the eutectic point.

The melting point increases as the molecular weight increases, and the

boiling point increases as the molecular size increases. The increase inmelting point is less regular than the increase in boiling point, becausepacking influences the melting point of a compound.

Polarity and solubility:Polarity

Is a physical property of a compound/drug , which relates other physicalProperties, e.g. melting and boiling points, solubility and intermolecularInteractions between molecules.

Generally, there is a direct correlation between the polarity of a molecule and the number andtypes of polar ornonpolar covalent bond that are present. In a few cases, a molecule having polar bonds,but in a symmetrical arrangement, may give rise to a no polarmolecule, e.g. carbon dioxide (CO2).

The polarity in a bond arises from the different electro negativities of thetwo atoms that take part in the bond formation. The greater the differencein electro negativity between the bonded atoms, the greater is the polarityof the bond. For example, water is a polar molecule, whereas cyclohexaneis non polar.


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H - OH CyclohexaneWater a polar molecule A non polar molecule

SolubilityIs the amount of a solute/drug that can be dissolved in a specific solvent

Under given conditions. The dissolved substance is called the solute and the

dissolving fluid is called the solvent, which together form a solution. Theprocess of dissolving is called solvation, or hydration when the solvent iswater. In fact, the interaction between a dissolved species and the moleculesof a solvent is solvation.The solubility of molecules/drugs can be explained on the basis of the polarityof molecules. Polar, e.g. water , ethanol , methanolNon-Polar, e.g. benzene , n-hexane , petroleum etherSolvents do not mix. In general, like dissolves like; i.e., materials with similar polarity are soluble in eachother. The hydrogen bonding and other non-bonding interactions between molecules.Refractive IndexThe refractive index (or index of refraction) of a medium is a measure for how much the speed of light

(or other waves such as sound waves) is reduced inside the medium. This is a very important propertyof a material or compound, that may characterize a purity or composition of a mixture. Refractive indexof a drug is a very important property of a drug product or API to know for the pharmaceuticalindustry because in many cases the size of drug particles are regulated. Existing laser particle sizecounters may actually estimate particle size if known the refractive index of the particle material.

Relative DensityRelative density, or specific gravity, is the ratio of the density (mass of a unit volume) of a substance tothe density of a given reference material. Specific gravity usually means relative density with respect towater. The term "relative density" is often preferred in modern scientific usage.If a substance's relative

density is less than one then it is less dense than the reference; if greater than 1 then it is denser thanthe reference.

Moisture1.0 g each of the respective powdered samples was weighed each on aluminum foil on the automatedmoisture analyzer pan and set at 105C for 3 h where moisture content percentage of the sample wasobtained (WHO, 1998).

Total ash2.0 g of the respective powdered samples was ignited in a previously ignited and tarred crucible at500C for about 3 h until the sample was white, indicating the absence of carbon, and was cooled in adesiccators and was later weighed (WHO, 1998).

Loss of weightLoss of weight of drug as moisture content evaporate and low volatile solvents also evaporate at giventemperature.03

Physicochemical properties of drugs in solution


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Activity and chemical potentialConcentration unitsThermodynamicsIonisation of drugs in solution05Characterization of a drug is as under:

CAFFEINECaffeineis a xanthine alkaloid compound that acts as a stimulant in humans. Caffeine is sometimescalled guaranine when found in guarana, mateine when found in mate, and theine when found in tea. Itis found in the leaves and beans of the coffee plant, in tea, yerba mate, and guarana berries, and in smallquantities in cocoa, the kola nut and the Yaupon Holly. Overall, caffeine is found in the beans, leaves,and fruit of over 60 plants, where it acts as a natural pesticide that paralyzes and kills certain insectsfeeding upon them.06

STRUCTURE OF CAFFEINE07
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CRYSTALLINE POWDER FORM OF CAFFEINE08

ISOLATION OF CAFFEINE1) To isolate caffeine from dry tea leaves by extraction and purify the crude extract by recrystallization.2) To determine the mass percentage of caffeine in the tea leaves09

Isolation of pure caffeineCaffeine isolation is an important industrial process and can be performed using a number of differentsolvents. Benzene, chloroform, trichloroethylene and dichloromethane have all been used over the yearsbut for reasons of safety, environmental impact, cost and flavor, they have been superseded by thefollowing main methods:

Water extraction/isolationCoffee beans are soaked in water. The water, which contains not only caffeine but also many othercompounds which contribute to the flavor of coffee, is then passed through activated charcoal, whichremoves the caffeine. The water can then be put back with the beans and evaporated dry, leavingdecaffeinated coffee with a good flavor. Coffee manufacturers recover the caffeine and resell it for use insoft drinks and medicines.

Supercritical carbon dioxide extraction/isolation


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Supercritical carbon dioxide is an excellent nonpolar solvent for caffeine (as well as many other organiccompounds), and is safer than the organic solvents that are used for caffeine extraction. The extractionprocess is simple: CO2 is forced through the green coffee beans at temperatures above 31.1 C andpressures above 73 atm. Under these conditions, CO2 is in a "supercritical" state: it has gaslikeproperties which allow it to penetrate deep into the beans but also liquid-like properties which dissolve97-99% of the caffeine. The caffeine-laden CO2 is then sprayed with high pressure water to remove the

caffeine. The caffeine can then be isolated by charcoal adsorption (as above) or by distillation,recrystallization, or reverse osmosis.10

Isolation by nonhazardous organic solventsOrganic solvents such as ethyl acetate present much less health and environmental hazard thanpreviously used chlorinated and aromatic solvents. The hydrolysis products of ethyl acetate are ethanoland acetic acid, both nonhazardous in small quantities. Another method is to use triglyceride oilsobtained

Physio Chemical Characterization of Caffeine1. Description : A white, crystalline powder or silky, white

crystals, sublimes readily.2. Solubility : Sparingly soluble in water, freely soluble in

boiling water, slightly soluble in ethanol. Itdissolves in concentrated solutions of alkali

benzoates or salicylates.3. Identification :A. Melting Point: 234 C to 239 CB. Infrared absorption spectrophotometryC,D. Chemical Test given by caffeine and alkaloids

Test for alkaloids1. Dragendorffs test1 ml of extract, add 1 ml of Dragendroffs reagent (potassium bismuth iodide solution). An orange-redprecipitate indicates the presence of alkaloids.2.Mayers test1 ml of extract, add 1 ml of Mayers reagent (potassium mercuric iodide solution). Whitish or creamcolored precipitate indicates the presence of alkaloids.3.Hagers test1 ml of extract, add 3 ml of Hagers reagent (saturated aqueous solution of picric acid). Yellow colored

precipitate indicates the presence of alkaloids4. Wagners test1 ml of extract, add 2 ml of Wagners reagent (iodine in potassium iodide). Reddish brown coloredprecipitate indicates the presence of alkaloids

E. Loss on dryingF. Reaction of xanthines4. Appearance of solution : To meet the test.5. Acidity : Not more than 0.2ml of 0.01M NaOH is required6. Related Substances : Thin-Layer Chromatography


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7. Sulphates : Not more than 500 ppm8. Heavy Metals : Not more than 10 ppm Pb9. Loss on drying : Not more than 0.5%10. Sulphated Ash : Not more than 0.1%

Ignition temperature >600 C

Solubility 20 g/l (20 C)Melting point 235 - 239 CMolar mass 194.19 g/molDensity 1.23 g/cm3 (18 C)Bulk density 300 - 600 kg/m3pH value 5.5 - 6.5 (10 g/l, H2O, 20 C)Vapor pressure 20 hPa (80 C)11

Physio Chemical Characterization of Caffeine in Tabulated Form12

Caffeine

General

Systematicname

1,3,7-trimethyl-1H-purine-2,6(3H,7H)-dione

Othernames

1,3,7-trimethylxanthine, trimethylxanthine,theine, mateine, guaranine,methyltheobromine

Molecularformula

C8H10N4O2

SMILES O=C1C2=C(N=CN2C)N(C(=O)N1C)C

Molar mass 194.19 g mol 1Appearance Odorless, white needles or powderCASnumber

[58-08-2]
http://en.wikipedia.org/wiki/Carbonhttp://en.wikipedia.org/wiki/Hydrogenhttp://en.wikipedia.org/wiki/Hydrogenhttp://en.wikipedia.org/wiki/Hydrogenhttp://en.wikipedia.org/wiki/Nitrogenhttp://en.wikipedia.org/wiki/Nitrogenhttp://en.wikipedia.org/wiki/Oxygenhttp://en.wikipedia.org/wiki/Oxygenhttp://en.wikipedia.org/wiki/Oxygenhttp://en.wikipedia.org/wiki/Oxygenhttp://en.wikipedia.org/wiki/Nitrogenhttp://en.wikipedia.org/wiki/Hydrogenhttp://en.wikipedia.org/wiki/Carbon


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Properties

Density andphase

1.2 g/cm, solid

Solubility inwater

Slightly soluble

Othersolvents

Soluble in ethyl acetate, chloroform, pyrimidine, pyrrole,tetrahydrofuran solution; moderately soluble in alcohol,acetone; slightly soluble in petroleum ether, ether,benzene.

Meltingpoint

237 C

Boilingpoint

178 C (sublimes)

Acidity(pKa)

10.4 (40 C)

Hazards

MSDS External MSDS

Mainhazards

May be fatal if inhaled, swallowedor absorbed through the skin.

Flash point N/ARTECSnumber

EV6475000

Except where noted otherwise, data are given formaterials in theirstandard state (at 25 C, 100 kPa)

Infobox disclaimer and references

Methods of Determination of CaffeineSeveral techniques have been reported for the individual quantification of caffeine as well assimultaneous determination of caffeine with different analytes in pharmaceutical preparations biologicalfluids and foodstuffs.

One of the earliest methods of caffeine determination is based up on ultraviolet (UV)spectrophotometry. Caffeine absorbs in the ultra violet region at 276 nm 13. Although spectrophotometryis a fast and simple method, it is not possible to determine caffeine directly in coffee beans by theconventional UV absorption due to the spectral overlap. On the other hand, the derivativespectrophotometer is relatively easy; however, it requires larger concentration of caffeine in thesamples13.

The more recent methods of caffeine determination are based on the high performance liquidchromatography (HPLC) combined with several detection methods like UV, mass and infraredspectrometry. However, most of these reported procedures involve relatively long retention times orrequire lengthy sample pretreatments14.

There are also other techniques reported for caffeine determination suchas

Fourier Transform Infrared spectroscopy Ion chromatography liquid chromatography coupled to mass spectrometry
http://www.sciencestuff.com/msds/C1410.htmlhttp://www.sciencestuff.com/msds/C1410.htmlhttp://en.wikipedia.org/wiki/Standard_statehttp://en.wikipedia.org/wiki/Standard_statehttp://en.wikipedia.org/wiki/Standard_statehttp://en.wikipedia.org/wiki/Wikipedia:Chemical_infoboxhttp://en.wikipedia.org/wiki/Wikipedia:Chemical_infoboxhttp://en.wikipedia.org/wiki/Wikipedia:Chemical_infoboxhttp://en.wikipedia.org/wiki/Standard_statehttp://www.sciencestuff.com/msds/C1410.html


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Nuclear magnetic resonance (NMR) spectroscopyNuclear magnetic resonance (NMR) spectroscopy is probably one of the most versatile analytical toolsavailable, and has become the technique of choice for biological fluids15 and polymer tests , and forpharmaceutical analysis. The latter includes the determination of impurities, the contents of drugs andthe characterization of isomeric drug mixtures 16.

Generally, NMR becomes quantitative NMR (qNMR) whenever it is applied as a quantitative analyticaltool. In principle, qNMR is amenable to all NMR-sensitive nuclei and unrestricted in dimensions.Quantitative proton NMR (qHNMR) is the most commonly used technique in the analysis of foods,pharmaceuticals, natural products, etc. Because the second most important studied organic NMRnucleus (13C) is less sensitive (1.6% of 1H sensitivity for an equal number of nuclei) and low naturalabundance (1.1%), it is difficult to obtain quantitative information by quantitative 13C NMR technique,especially for small natural product samples.

Besides qualitative information, NMR can provide quantitative information about the sample since theintensity (or the area) of a sample is directly proportional to the number of nuclei producing the signal.The precision of the integrals determines the accuracy of quantification, which depends on the noise

level of the spectrum, the line shape, quality of shimming and phase-, baseline- and drift corrections16.

For simple compositional analysis, integration of the spectrum or selected spectral region is performed,followed by adjustment of the integrated intensities to reflect the number of protons giving rise to theintegrated signals. The individual integrated intensities are summed and then expressed as a percent ofsummed integrations, which represents the molar composition of the mixture (mole%). If an absolutedetermination of the principal component of a complex mixture is required, it is necessary to develop aweight-percent quantitative assay. This procedure would involve obtaining a weight (mg) of a sampleof the crude mixture, adding a precise quantity of a known internal standard, obtaining the solutionqHNMR spectrum of the sample plus internal standard and calculating the actual weight of the desiredcomponent of the crude mixture.

Advantage of using NMR SpectroscopyThe main advantage of using NMR for quantitative analysis is that it is simple and straightforward. Inmost applications, the sample only has to be dissolved in a deuterated solvent followed by measurementof NMR spectrum. Ideally, every signal in the NMR spectrum has the same response factor concerningthe number of magnetically equivalent nuclei that constitute the signal, which make the calculationsimple 16,17. Other advantages of NMR are its nondestructive nature and selectivity, together with the factthat it reveals structural information about previously known contaminants that may be present.

Thin-layer chromatography (TLC)Thin-layer chromatography (TLC) is a very old method of analysis that has been well proven in practice.

For more than thirty years, it has occupied a prominent position, especially in qualitative investigations.With the development of modern pre-coated layers and the introduction of partially or completelyautomated equipments for the various stages of operation of TLC, not only are highly accuratequantitative determinations now possible, but also the requirements that the work should comply withgood manufacturing practice (GMP)/ good laboratory practice (GLP) guidelines can be fulfilled.


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Thin layer chromatography can be applied in different areas of analysis: pharmaceuticals and drugs,clinical chemistry, forensic chemistry, biochemistry, food analysis, environmental analysis, naturalproducts chemistry, synthetic organic chemistry and other areas.18

Quantitative TLC Analysis of CaffeineDevelopment of the Optimum Mobile PhaseThe TLC procedure was optimized with a view to quantify caffeine in the coffee, tea and soft drinkextracts. The mobile phase consisting of chloroform and methanol (10:1 v/v) gave a good resolution, anda sharp and well-defined peak at Rf=0.64 for caffeine in the standard as well as in the extracts (Figure 3). Well-defined spots were obtained when the developing chamber was saturated for 10 minutes at roomtemperature. This enables us to accurately quantify caffeine in dilute solutions.

Figure 3. TLC of caffeine standard and two extracts developed with chloroform, methanol (10:1). Left toright: Tracks 1, 2, 4, 6 represent 200, 500, 800, 1100 ng caffeine standard respectively; tracks 3 and 5represent 500 ng tea and 450 ng coffee extracts,

Quantitative 1H NMR Analysis of Caffeine

Qualitative AnalysisThe spectrum of caffeine (1) consists of three sharp singlets at 3.22, 3.40 and 3.83 due to the three

methyl groups connected to the nitrogen atoms as well as a singlet peak at 7.78 corresponding to the

=C-H proton.It should be noted that, in all spectra in Figure 2, a sharp singlet peak is observed at 4.70corresponding to water.


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Figure 2. Proton NMR spectra of caffeine

REFERENCES


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01.Www.Google.com.

02.Drug Characterization/Impurity Profiling, Scientific Sec. page 1-9.

03.Ebbing, D. D. and Gammon, S. D. General Chemistry, 7th edn, Houghton Mifflin, New York, 2002.04.Www.ssci-inc.com

05. Physicochemical Principles of Pharmacy, 4th edition (ISBN: 0 85369 608 X) Pharmaceutical Press200606.Lovett, Richard (24 September2005). "Coffee: The demon drink?". New Scientist(2518).

07.Brain, Marshall, and Charles W. Bryant. "How Caffeine Works." HowStuffWorks. 01 Apr 2000. Web.4 Jun 2010. .

08.Www.Tajapi.com

09.Www.Chemistry.Sc.Chula.ac.th/bsac.....2012/Exp.4[1].

10. Smit, HJ; Gaffan EA, Rogers PJ. (2004 Nov). "Methylxanthines are the psycho-pharmacologicallyactive constituents of chocolate". Psychopharmacology176 (3-4): 412-9.11. World Health Organizational (1998).Quality Control Methods for Medicinal Plant Materials, WHOGeneva Switzerland. Materials, WHO Geneva Switzerland, p. 128.

12.Caffeine Content of Food and Drugs.Nutrition Action Health Newsletter. Center For Science in thePublic Interest (December 1996). Retrieved on2006-08-22.

13.Perrone, D., Donangelo, C. M., Farah, A., 2008. Fast simultaneous analysis of caffeine, trigonelline,nicotinic acid and sucrose in coffee by liquid chromatography-mass spectrometry. Food Chemistry110,1030-1035.a

14. Abebe, B., Kassahun, T., Mesfin, R., Araya, A., 2008. Measurement of caffeine in coffee beans withUV/vis spectrometer. Food Chemistry108, 310-315.a15. Nicholas, P. C., Kim, D., Crews, F. T., Macdonald, J. M., 2006. Proton nuclear magnetic resonancespectroscopic determination of ethanol-induced formation of ethyl glucuronide in liver. AnalyticalBiochemistry358, 185-191.a16. Pauli, G. F., Jaki, B. U., Lankin, D. C., 2005. Quantitative 1H NMR: development and potential of amethod for natural products analysis.Journal of Natural Products68, 133-149.a17.Forshed, J., Erlandsson, B., Jacobsson, S. P., 2005. Quantification of aldehydes impurities inpoloxamer by 1H NMR spectroscopy. Analytica Chimica Acta552, 160-165.a37
http://en.wikipedia.org/wiki/September_24http://en.wikipedia.org/wiki/September_24http://en.wikipedia.org/wiki/2005http://en.wikipedia.org/wiki/2005http://en.wikipedia.org/wiki/2005http://www.dialagranny.com/media/coffeens.pdfhttp://www.dialagranny.com/media/coffeens.pdfhttp://www.dialagranny.com/media/coffeens.pdfhttp://health.howstuffworks.com/caffeine.htmhttp://health.howstuffworks.com/caffeine.htmhttp://health.howstuffworks.com/caffeine.htmhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15549276http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15549276http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15549276http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15549276http://www.cspinet.org/nah/caffeine/caffeine_content.htmhttp://www.cspinet.org/nah/caffeine/caffeine_content.htmhttp://www.cspinet.org/nah/caffeine/caffeine_content.htmhttp://en.wikipedia.org/wiki/2006http://en.wikipedia.org/wiki/2006http://en.wikipedia.org/wiki/August_22http://en.wikipedia.org/wiki/August_22http://en.wikipedia.org/wiki/August_22http://en.wikipedia.org/wiki/August_22http://en.wikipedia.org/wiki/2006http://www.cspinet.org/nah/caffeine/caffeine_content.htmhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15549276http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15549276http://health.howstuffworks.com/caffeine.htmhttp://www.dialagranny.com/media/coffeens.pdfhttp://en.wikipedia.org/wiki/2005http://en.wikipedia.org/wiki/September_24


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18. Hahn-Deintrop, E., 2000. Applied thin-layer chromatography: best practice and avoidance of mistakes.Willey-VCH, Weinhein, Germany, pp. 54-153.d

Characterization of Drugs

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