`
`3.
`
`Preparation Instructions
`The solubility in ethanol is 1 g in 66 ml (approx.
`15 mg/ml).1 Caffeine is also soluble in water (approx.
`16 mg/ml at room temperature, 200 mg/ml at 80(cid:176) C, or
`666 mg/ml in boiling water. Solubility in water is
`increased by adding dilute acid (e.g. HCl or citric
`acid).1,4 Caffeine is decomposed by strong bases.4
`
`Storage/Stability
`Stored at room temperature this product has a shelf-life
`of 4 years. Solutions in organic solvents (e.g. methanol
`or ethanol) are stable at 2-8(cid:176) C for several years. 5
`
`References
`1. Merck Index, 12th Ed., #1674 (1996).
`2. Zubair, M.U. et al., Analytical Profiles of Drug
`Substances, Vol. 15, K. Florey, ed. (Academic
`Press, 1986), pp 71-150.
`Instrumental Data for Drug Analysis, 2nd Ed., eds.
`T. Mills et al., (Elsevier Press, 1991) p. 296.
`4. Clarke's Isolation and Identification of Drugs, 2nd
`Ed., ed. A.C. Moffatt et al., (Pharmaceutical Press,
`1986), p. 421-423.
`5. Sigma quality control data.
`6. Supplier information.
`7. Snyder, S.H. et al., Proc. Natl. Acad. Sci. USA, 78,
`3260-3264 (1981).
`8. Schwabe U. et al., Naunyn Schmiedebergs Arch.
`Pharmacol., 330, 212-221 (1985).
`9. Kemp, R.G., and Huang, Y.-C., Methods in
`Enzymol., 38, 240-244 (1974).
`10. Shafer, S.H. et al., Biochem Pharmacol., 56, 1229-
`1236 (1998).
`11. Islam, M.S. et al., Proc. Natl. Acad. Sci. USA, 95,
`6145-6150 (1998).
`12. He, A.W., and Cory, J.G., Anticancer Res. 19, 421-
`428 (1999).
`13. Poe, B.S., and O'Neill, K.L., Cancer Lett., 121, 1-6
`(1997).
`14. Traganos, F. et al., Cancer Res., 53, 4613-4618
`(1993).
`15. Takagi M. et al., Leukemia, 13, 70-77 (1999).
`16. Link, C.J. Jr. et al., Carcinogenesis, 16, 1149-1155
`(1995).
`
`alc 5/17/99
`
`
`
`Sigma brand products are sold through Sigma-Aldrich, Inc.
`Sigma-Aldrich, Inc. warrants that its products conform to the information contained in this and other Sigma-Aldrich publications. Purchaser
`must determine the suitability of the product(s) for their particular use. Additional terms and conditions may apply. Please see reverse side of
`the invoice or packing slip.
`
`
`
`CAFFEINE (ANHYDROUS)
`Product Number C0750
`Storage Temperature RT
`
`
`CAS #: 58-08-2
`Synonyms: 1,3,7-trimethylxanthine;
`Methyltheobromine; 3,7-dihydro-1,3,7-trimethyl-1H-
`purine-2,6-dione
`
`
`C H 3
`
`NN
`
`H 3C
`
`N
`
`O
`
`O
`
`N
`
`C H 3
`Product Description
`Appearance: white powder
`Molecular Formula: C8H10N4O2
`Molecular Weight: 194.2
`Melting point: 238(cid:176) C1
`Sublimes above 178(cid:176) C at atmospheric pressure, but
`will sublime at 160-165(cid:176) C at 1 mm Hg
`Extensive analytical data have been published.2-4
`pKa = 14.0 at 25(cid:176) C4
`EmM(272 nm) = 9.3-9.4 (0.1 M HCl)5
`The product is synthetic, prepared according to the
`Taub synthesis method. 6
`
` A
`
` popular central nervous system (CNS) stimulant.
`Caffeine is a well-known drug commonly used as a mild
`stimulant, found in dietary sources such as coffee, tea,
`and cocoa. It is believed to act through adenosine
`receptors and monoamine neurotransmitters.7 It is an
`adenosine receptor antagonist and adenosine 3',5'-
`cyclic monophosphate (cAMP) phosphodiesterase
`inhibitor.8,9 Thus, levels of cAMP increase in cells
`following treatment with caffeine.10 It has been reported
`to affect cellular calcium levels, releasing calcium from
`intracellular stores.11 It overrides the cell cycle effects
`of various chemicals such as protease inhibitors,
`thereby preventing apoptosis12-14; and it has been
`shown to inhibit cellular DNA repair mechanisms .15,16
`
`Precautions and Disclaimer
`Keep tightly sealed.
`
`
`Page 1
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`Mylan v. MonoSol
`IPR2017-00200
`MonoSol Ex. 2026
`
`