Chapter-8 Caffeine Department of Chemistry, Dr. Hari Singh Gour Central University, Sagar (M.P.) 186 Introduction – Caffeine is a pharmacologically active substance and depending on the dose, can be a mild central nervous system stimulant. Caffeine does not accumulate in the body over the course of time and is normally excreted within several hours of consumption [1-2]. In humans, caffeine acts as a central nervous system stimulant, temporarily warding off drowsiness and restoring alertness. It is the world's most widely consumed psychoactive drug, but, unlike many other psychoactive substances, it is both legal and unregulated in nearly all parts of the world [3]. Structure - IUPAC Name - 3, 7-dihydro-1, 3, 7-trimethyl-1H-purine-2,6-dione. - 1, 3, 7,-Trimethylxanthine. - 1, 3, 7-Trimethyl-4, 6-dioxopurine Formula - C 8 H 10 N 4 O 2 Solubility - Freely soluble in chloroform, methanol and in boiling water; sparingly soluble in water and in ethanol (95 per sent) Mol. Wt. - 194.19 Brand Name - Vivarin-200 mg [A] - Stay awake-200 mg [B] - Ra stay awake-200 mg [C] Identification - Identification of pure drug is performed by FT-IR (Shimadzu 8400s) and compared with standard one [4].
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Chapter-8 Caffeine
Department of Chemistry, Dr. Hari Singh Gour Central University, Sagar (M.P.) 186
Introduction – Caffeine is a pharmacologically active substance and
depending on the dose, can be a mild central nervous system
stimulant. Caffeine does not accumulate in the body over the course
of time and is normally excreted within several hours of consumption
[1-2].
In humans, caffeine acts as a central nervous system stimulant,
temporarily warding off drowsiness and restoring alertness. It is the
world's most widely consumed psychoactive drug, but, unlike many
other psychoactive substances, it is both legal and unregulated in
nearly all parts of the world [3].
Structure -
IUPAC Name - 3, 7-dihydro-1, 3, 7-trimethyl-1H-purine-2,6-dione.
- 1, 3, 7,-Trimethylxanthine.
- 1, 3, 7-Trimethyl-4, 6-dioxopurine
Formula - C8H10N4O2
Solubility - Freely soluble in chloroform, methanol and in
boiling water; sparingly soluble in water and in
ethanol (95 per sent)
Mol. Wt. - 194.19
Brand Name - Vivarin-200 mg [A]
- Stay awake-200 mg [B]
- Ra stay awake-200 mg [C]
Identification - Identification of pure drug is performed by FT-IR
(Shimadzu 8400s) and compared with standard
one [4].
Chapter-8 Caffeine
Department of Chemistry, Dr. Hari Singh Gour Central University, Sagar (M.P.) 187
Wave number (cm-1)
Fig. 8.1: Reference IR Spectrum of CFI
Fig. 8.2: IR Spectrum of pure CFI
Chapter-8 Caffeine
Department of Chemistry, Dr. Hari Singh Gour Central University, Sagar (M.P.) 188
Table 8.1: Characteristics absorption frequencies for identification of
pure CFI
S. No. Types of Vibrations Frequency (cm-1) 1. Ar. C – H Stretching 3113.21
2. Ar. C – H Bending 758.05
3. C – N Stretching 1359.86
4. C = O Stretching 1697.41
5. C = N 1599.04
6. Ar. C - C Stretching 1604.83
Bioavailability - 99%
Protein binding - 17% to 36%
Metabolism - Caffeine is metabolized in the liver into three primary
metabolites, paraxanthine (84%), theobromine (12%) and theophylline
(4%). Caffeine from coffee or other beverages is absorbed by the small
intestine within 45 minutes of ingestion and then distributed
throughout all tissues of the body [5]. Peak blood concentration is
reached within one hour [6]. Caffeine can also be absorbed rectally,
evidenced by the formulation of suppositories of ergotamine tartrate
and caffeine (for the relief of migraine) [7], chlorobutanol and caffeine
(for the treatment of hyperemesis) [8]. Caffeine is metabolized in
the liver by the cytochrome P450 oxidase enzyme system (to be specific,
the isozyme) into three metabolic dimethylxanthines [9].
Half – Life - 5 hrs
Excretion - urine
History - Caffeine was first isolated from coffee in 1820 by the German
chemist Friedlieb Ferdinand Runge, and then independently in 1821
by French chemists Pierre Robiquet, Pierre Pelletier, and Joseph
Caventou. Pelletier coined the word "caffeine" from the French word
for coffee (café), and this term became the English word "caffeine".
Chapter-8 Caffeine
Department of Chemistry, Dr. Hari Singh Gour Central University, Sagar (M.P.) 189
The history of coffeine has been recorded as far back as the
ninth century. During that time, coffee beans were available only in
their place of origin, Ethiopia. Legends trace the discovery of coffee
either to a Sufi dervish named Omar, or to a goatherder named Kaldi,
who observed goats become elated and sleepless at night after grazing
on coffee shrubs and, upon trying the berries the goats had been
eating, experienced the same vitality [10].
In 1819, the German chemist Friedlieb Ferdinand Runge isolated
relatively pure caffeine for the first time; he called it "Kaffebase" (i.e.,
a base that exists in coffee) [11].
The structure of caffeine was elucidated near the end of the 19th
century by Hermann Emil Fischer, who was also the first to achieve
its total synthesis. This was part of the work for which Fischer was
awarded the Nobel Prize in 1902 [12].
Use - Caffeine which is found in tea and coffee imparts bitterness and
also acts as a flavor constituent. It is a mild nervous stimulant
towards drowsiness and fatigue. Caffeine is used as a drug on the
basis of its effect on respiratory, cardiovascular and the central
nervous system. It is included with ergotamine in some anti-migraine
preparations, the object being to produce a mildly agreeable sense of
alertness. Caffeine is administered in the treatment of mild respiratory
depression caused by central nervous system depressants such as
narcotic.
Adverse effect - Common adverse effects include drowsiness,
headaches, migraines, confusion, Incontinence and liver damage.
Bio–Analytical methods -
Several methods have been reported for the determination of
CFI standards and in pharmaceutical preparations.
B. B. Fredholm et al., have described the actions of caffeine in
the brain with special reference to factors that contribute to its
widespread use [13].
Chapter-8 Caffeine
Department of Chemistry, Dr. Hari Singh Gour Central University, Sagar (M.P.) 190
A. Astrup et al., have studies caffeine a double-blind, placebo
controlled study of its thermogenic, metabolic, and cardiovascular
effects in healthy volunteers [14].
J. M. Kalmar et al., have introduced the effects of caffeine on
neuromuscular function [15].
E. Hogervorst et al., have described the caffeine improves
physical and cognitive performance during exhaustive exercise [16].
I. Hindmarch, et al., have studied the effects of black tea and
other beverages on aspects of cognition and psychomotor performance
[17].
M. Johnson-Kozlow, et al., have described the coffee consumption
and cognitive function among older adults [18].
M. Kivipelto, et al, introduced the midlife vascular risk factors
and Alzheimer's disease in later life: longitudinal, population based
study [19].
C. A. Manning, et al., have studied the glucose enhancement of
24-h memory retrieval in healthy elderly humans [20].
P. J. Mitchell, et al., have described the effects of caffeine, time
of day and user history on study-related performance [21].
Caffeine an alkaloid of the methylxanthine family is a naturally
occurring substance found in the leaves, seeds or fruits of over 63
plants species worldwide. The most commonly known sources of
caffeine are coffee, cocoa beans, cola nuts and tea leaves. In its pure
state, it is an intensely bitter white powder. Various manufacturers
market caffeine tablets, claiming that using caffeine of pharmaceutical
quality improves mental alertness. These effects have been borne out
by research that shows that caffeine use results in decreased fatigue
and increased attentiveness [22].
Chapter-8 Caffeine
Department of Chemistry, Dr. Hari Singh Gour Central University, Sagar (M.P.) 191
Determination of λmax using solvent
The pure form of CFI was accurately weighed 10 mg and
dissolved in 100 mL of medium (PEG 4000 9× 10-5 M). The Stock
solution 100 μg/mL was further diluted 1.0 mL in 100 mL media to
give a concentration of 1 μg/mL, the absorption spectra were obtained
with Elico 164 UV-Visible double beam spectrophotometer a scan
range of 200-400 nm and determine the maximum absorbance of drug
at λmax 270 nm. (Fig. 8.3.)
Fig. 8.3: Determination of λmax
using solvent
Determination of calibration curve using solvent
The stock solution (100 μg/mL) of CFI was prepared by
dissolving 10 mg of CFI in 100 mL volumetric flask and made upto