Caffeine Acetylsalicylic acid

Gamiz-Gracia, L. and De Castro, M. D. L. An HPLC method for the determination of vitamin Bl, caffeine, acetylsalicylic acid, and the impurities of salicylic acid in a pharmaceutical preparation. J. Liq. Chromatogr. Relat. Technol. 20 2123-2133, 1997. 

This experiment focuses on developing an HPLG separation capable of distinguishing acetylsalicylic acid, paracetamol, salicylamide, caffeine, and phenacetin. A Gjg column and UV detection are used to obtain chromatograms. Solvent parameters used to optimize the separation include the pH of the buffered aqueous mobile phase, the %v/v methanol added to the aqueous mobile phase, and the use of tetrabutylammonium phosphate as an ion-pairing reagent. 

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). 

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. 

This example will illustrate the quantitative analysis of aspirin (acetylsalicylic acid), phenacetin and caffeine in a mixture. The structures of these three are shown in Fig. 4.4a. 

Following the development of the test, an in-house validation was conducted to evaluate the performance of FETAX compared to the results in the rat and/or rabbit. Thirteen reference chemicals were tested including eight compounds known to be teratogenic in rats and/or rabbits (caffeine, retinoic acid, hydroxyurea, ethanol, cyclophosphamide, nicotine, acetylsalicylic acid, dexametha-sone) and five non-teratogens (isoniazid, saccharin, paracetamol, penicillin G, sildenafil). The estimation of teratogenicity in rats and rabbits was based on published data (9). 

The same experimental setup was used in the separation of metabolites of paracetamol from a human urine extract [73] and Thomapyrin, containing acetaminophen, caffeine, and acetylsalicylic acid [74], Compared to isocratic CEC—NMR, gradient CEC—NMR offers increased sample loading capacity because of preconcentration at the front of the column and higher separation efficiency together with a reduction in analysis time [75],... 

APC tablet (aspirin, phenacetin, caffeine, any supplier). If these tablets are not available, a laboratory mixture may be prepared by mixing 226.8 mg of acetylsalicylic acid (aspirin), 32.4 mg of caffeine, and 162 mg of phenacetin for this experiment. This laboratory mixture will suffice as an APC tablet. ... 

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-... 

Thomapyrin, containing acetaminophen, caffeine, and acetylsalicylic acid Antiviral drug suramin... 

Figure 32 Single rows extracted from the continuous-flow CEC separation shown in Figure 32B (A) acetaminophen (at 48-52 min) (B) caffeine (at 54-58 min) (C) acetylsalicylic acid (at 62-65 min). (Reprinted from Ref. 132, with permission.)...

Acetylsalicylic Acid-Acetaminophen-Caffeine Tablet (250mg + 250mg +... 

FIGURE 7 Dissolution profile for acetylsalicylic acid-acetaminophen-caffeine tablet (250mg + 250mg + 50mg) paddle 50rpm, 37°C deionized water. 

Acetylsalicylic acid, caffeine, paracetamol/ plasma, urine HPLC UV Column pBondapak Cjg (300 X 3.9 mm, 10 pm) Mobile phase Solvent A ACN Solvent B water (gradient elution) Detection 2 = 280 nm Extraction SPE/column Cig/elution MeOH LOD 0.1-0.2 pg/ mL LOQ 0.15-0.2 pg/ mL [77]... 

Abu-Qare, A.W., Abou-Donia, M.B. A validated HPLC method for the determination of pyridostigmine bromide, acetaminophen, acetylsalicylic acid and caffeine in rat plasma and urine. J. Pharm. Biomed. Anal. 26, 939-947 (2001)... 

Acetylsalicylic acid, benzoic acid, caffeine, sodium benzoate... 

A 72-year-old man developed a generalized maculo-papular rash 12 hours after taking co-codamol (codeine 10 mg plus paracetamol 500 mg) (8). The lesions persisted for 7 days, became scaly, and disappeared. He later reported a similar skin condition after having taken a combination of acetylsalicylic acid, codeine, and caffeine. Patch tests gave a positive result for codeine, suggesting a type IV allergic reaction. 

Cross reactivity (S22I) At a concentration of 1000 mg/1 in serum the following compounds increased the apparent value for a 30 mg/1 phenobarbital control by < 20% acetaminophen, acetylsalicylic acid, caffeine, carbamazep-ine, diazepam, ethosuximide, fluphenazine, hexabarbital, indomethacin, meprobamate, methaqualone, methsuximide, methyprylon, phenylbutazone, phensuximide, theophylline, and valproic acid. 

Acetylsalicylic acid Ascorbic acid Bromoisovalerylurea Caffeine... 

In 1963 Hoffman and Mitchell described a method for determining in a single run the active ingredients in APC-tablets (= Acetylsalicylic acid, Phenacetin, Caffeine tablets). Due to the high ratio of phenacetin to caffeine (162 mg 32 mg) and the small differences in their retention times, it was not very satisfactory for the determination of caffeine. However, the means of several analyses yielded results close to either the labeled claim or the composition by synthesis. The results of a series of analyses of synthetic APC mixtures are listed in Table 20.3. 

Figure 26-19 Flow-injection apparatus for the determination of caffeine in acetylsalicylic acid preparations. With the valve rotated at 90 deg, the flow in the bypass is essentially zero because of its small diameter. R and L are Teflon coils with 0.8-mm inside diameters L has a length of 2 m, and the distance from the injection point through P to the mixing point is 0.15 m. (Adapted from B. Karlberg and S. Thelander, Anal. Chim. Acta, 1978, 98, 2. Reprinted with permission from Elsevier.)...

Figure 18.13 Optimized chromatogram of a six-component mixture with acids and bases [reproduced with permission from Y. Hu and D.L. Massart, J. Chromatogr., 485, 311 (1989)]. Conditions column, 25cm x 4mm i.d. stationary phase, LiChrosorb RP18 5ixm mobile phase, 1 ml min methanol-phosphate buffer pH 3.0 (1 1) UV diode array detector. Peaks 1 = paracetamol 2 = acetylsalicylic acid 3 — caffeine 4 = benzocaine 5 = carbamazepine 6 = propyphenazone.

Mamolo, M.G. Vio, L. Maurich, V. High-pressure liquid chromatographic analysis of paracetamol, caffeine and acetylsalicylic acid in tablets. SaU( lic acid quantitation. Farmaco.[Prat]., 1985, 40, 111-123... 

Lau, A.H. Chang, C.W. Schlesinger, P.K. Evaluation of a potential drug interaction between sucralfate and aspirin. Clin.Pharmacol.Ther, 1986, 39, 151-155 [plasma pharmacokinetics extracted metabolites, salicylic acid, salicyluric acid a-phenylcinnamic acid (IS) gradient column temp 30] Mamolo, M.G. Vio, L. Maurich, V. Higb-pressure liquid chromatographic analysis of paracetamol, caffeine and acetylsalicylic acid in tablets. Salicylic acid quantitation. Farmaco.[Prat]., 1985, 40, 111— 123 [tablets simultaneous ac etcuninophen, caffeine, phenazone, salicylic acid]... 

Acetic acid Acetylsalicylic acid Alpha-Tocopherol Aluminum Hydroxide Aluminum Potassium Sulfate Aluminum Oxide Ammonium Hydroxide Ammonium Nitrate Ammonium Sulfate Amoxicillin Amyl Acetate Amyl Nitrite Ascorbic Acid Benzoic Acid Boric Acid Butyl Acetate Butylated Hydroxyanisole and Butylated Hydro-xytoluene Caffeine... 

Trinitrotoluene Acetaminophen Acetic acid Acetylene Acetylsalicylic acid Alpha-Tocopherol Amoxicillin Amyl Acetate Amyl Nitrite Ascorbic Acid Benzene Benzoic Acid Beta-Carotene Butane Butyl Acetate Butyl Mercaptan Butylated Hydroxyanisole and Butylated Hydroxytoluene Caffeine Camphor... 

Solvents (a) phosphate buffers contain AR Na2HP04 and NaH2P04 (0.025 M), pH adjusted to requirements using NaOH or H3PO4 (b) tetra-butyl ammonium phosphate (0.005 M) buffered to pH 7.6 (c) 1% HOAc. Mixture A acetylsalicylic acid (86 mg) paracetamol (5.1 mg) salicylamide (87.8 mg) caffeine (28.1 mg) phenacetin (11.4 mg) in 50 ml of methanol salicylic acid (6 mg) may be included because of the likelihood of its presence as an impurity in aspirin. 

Abu-Qare, A. W., and Abou-Donia, M. B. (2(H)la). A validated HPLC method for the dcicrminatioii of pyridostigmine bromide, acetaminophen, acetylsalicylic acid and caffeine in rat plasma and urine. J. Pharm. Biol. Ana . 26(5/6), 939-947. Abu-Qare. A. W, and Abou-Donia, B. M. (2001b). Simultaneous analyses of sarin, pyridostigmine bromide and their metabolites in rat plasma and urine using HPLC. Chwmawgraphia 53(5/6), 251-255. 

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