Caffeine Acetaminophen

Students determine the concentrations of caffeine, acetaminophen, acetylsalicylic acid, and salicylic acid in several analgesic preparations using both CZE (70 mM borate buffer solution, UV detection at 210 nm) and HPLC (C18 column with 3% v/v acetic acid mixed with methanol as a mobile phase, UV detection at 254 nm). 

A trademark for acetaminophen is Tylenol . Excedrin is acetaminophen, aspirin, and caffeine. Acetaminophen is easily synthesized from phenol. 

Gradient elution is an important and widely used technique to achieve faster and/or better separation of complex mixtures. The power of gradient elution has been realized with CEC-NMR while successfully analyzing an analgesic mixture containing caffeine, acetaminophen, and acetylsalicylic acid [58], Under isocratic conditions (2 mM borate, 80% D20, and 20% CD3CN), poorly separated peaks with a solvent peak-eluting close to acetaminophen are ob-... 

Unsupervised analyses are often performed on unknown samples in order to obtain qualitative results. The results shown in Figure 11.9 can be considered the final results here, the sample consisted of at least four chemical components-caffeine, acetaminophen, aspirin and cellulose-and their distributions were visualized in Raman images. 

Ou, C.-N. Frawley, V.L. Theophylline, dyphylline, caffeine, acetaminophen, sedicylate, acetylsaUcylate, procainamide, and N-acetylprocainamide determined in serum with a single Uquid-chromatographic assay. Clin.Chem., 1982, 28, 2157-2160... 

Repeat experiment 3.12 with caffeine, acetaminophen, or butyl acetate. 

Milling of the caffeine-acetaminophen mixture improved the determination of acetaminophen, but caffeine was imchanged. The difference between theoretical and predicted concentrations was 0.25%, competitive with HPLC. Near infrared allowed rapid analysis times with no expense for solvent purchase and disposal. 

The investigation of the effects of milling showed that this sample preparation procedure did not necessarily improve results. Milling of the caffeine-acetaminophen mixture significantly improved the determination of acetaminophen, but the determination of caffeine was virtually unchanged. The largest differences between the NIR determined concentrations and theoretical concentrations were attributed to sample handling variability. 

The analysis of APC tablets (a mixture of aspirin, phenacetin, and caffeine) has been a common undergraduate laboratory experiment. This experiment describes modifications to the standard analysis for APC tablets in which paracetamol (also known as acetaminophen) replaces phenacetin. 

Examples of the application of HPLC to the analysis of (a) acetaminophen, salicylic acid, and caffeine (b) chlorinated pesticides (c) tricyclic antidepressants and (d) peptides. (Chromatograms courtesy of Alltech Associates, Inc. Deerfield, IL). 

Skeletal Muscle Relaxant Combinations Carisoprodol Compound—carisoprodol, aspirin Mexaphen—chlorzoxazone, acetaminophen Lobac—salicylamide, phenyltoloxamine, acetaminophen Norgesic Fbrte—orphenadrine citrate, aspirin, caffeine Norgesic—orphenadrine citrate, aspirin, caffeine Robaxisal—methocarbamol, aspirin Sodol Compound—carisoprodol, aspirin Soma Compound—carisoprodol, aspirin... 

As the solvent mixture also contained 225 mg of tetramethyl ammonium hydroxide pentahydrate per liter at a high water content (75%), the surface of the reverse phase would have been largely covered with the tetramethyl ammonium hydroxide pentahydrate. This would have acted as an adsorbed ion exchange stationary phase. It is clear that the free acids, salicylic acid, acetylsalicylic acid (aspirin) and benzoic acid were retained largely by ionic interactions with adsorbed basic ion exchanger and partly by dispersive interactions with the exposed reversed phase. The acetaminophen and the caffeine, on the other hand, being unionized substances, were retained only by dispersive interactions with the exposed reversed phase. 

Similar methods with modifications such as the one by Schutz et al.8 have been in use for over 20 years. In 1968, Ferren and Shane9 published a paper on the differential spectrometric determination of caffeine in soluble coffee and drug combinations. It had the advantage of eliminating a preliminary separation that was required by the earlier method. While the method was successful for coffee, it was not as successful in the determination of caffeine in acetaminophen/phenacetin/caffeine tablets. They proposed that phenacetin was a limiting factor. The official AOAC methods for these methylxanthines in coffee and tea still involve similar methods.10... 

Proceeding along a parallel track, Guillory and coworkers used DTA analysis to study complexation phenomena [2]. Through the performance of carefully designed studies, they were able to prove the existence of association complexes and deduced the stoichiometries of these. In this particular work, phase diagrams were developed for 2 1 deoxycholic acid-menadione, 1 1 quinine-phenobarbital, 2 1 theophylline-phenobarbital, 1 1 caffeine-phenobar-bital, and 1 1 atropine-phenobarbital. The method was also used to prove that no complexes were formed between phenobarbital and aspirin, phenacetin, diphenylhydantoin, and acetaminophen. 

Aspirin or acetaminophen with butalbital, caffeine Isometheptene 65 mg/dichloralphenazone 100 mg/acetaminophen 325 mg (Midrin) Nonsteroidal antiinflammatory drugs... 

The combination of acetaminophen, aspirin, and caffeine is approved in the United States for relieving migraine pain and associated symptoms. 

N-demethylation at the three N-methyl sites. In this regard, the 3-N-demethylation of caffeine to generate paraxanthine can serve as a particularly good in vivo indicator of the presence and activity of CYP1A2 (Fig. 4.7). In the case of phenacetin, CYP1A2 catalyzes N-deethylation to generate acetaminophen. Not unexpectedly, 1 A2 s selectivity toward heterocyclic aromatic substrates carries over to inhibitors of the enzyme. Furafylline (Fig. 4.7) is an example of a particularly potent 1A2 mechanism-based inhibitor. 

Caffeine alone may produce analgesic effects in some forms of pain, but clinically it is most often used as an adjuvant medication (Laska et al. 1983 Ghelardini et al. 1997 Kraetsch et al. 1996 Forbes et al. 1991). It enhances the analgesic effects of nonsteroidal anti-inflammatory drugs such as acetaminophen and also speeds the onset of analgesia. It is effec-... 

Laska EM, Sunshine A, Zighelboim I, Roure C, Marrero I, Wanderling J, Olson N. (1983). Effect of caffeine on acetaminophen analgesia. Clin Pharmacol Then 33(4) 498-509. 

To demonstrate the ability to evaluate intersample variations, an over-the-counter (OTC) pain relief medication from two different manufacturers was compared. The samples contain three APIs each acetaminophen, aspirin and caffeine. Pure acetaminophen, aspirin and caffeine samples are obtained in either tablet form or powder compact and included within the same FOV as the tablets to provide simultaneous reference materials for the tablet samples. The tablets and pure components were arranged as shown in Plate 8.1a. Measurements on all samples were collected simultaneously. Tablet A samples from one manufacturer have a reported label concentration of 37%, 37%, and 10%, for the three API components, respectively. Tablet B samples from the second manufacturer contain the same three APIs, at label concentrations of 39%, 39%, and 10 %, respectively. In addition to these samples, tablet C samples are included in the array of tablets. These samples contain only acetaminophen as the API with a reported label concentration of 79%, and are made by the manufacturer who produces tablet A. The remaining mass of all three tablet types represents the excipient (binder, disintegrant, and lubricant) materials. 

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