Phenacetin tablets

Fig. 13 Rate of dissolution of phenacetin from powder, granules, and tablets in diluted gastric juice (Surface Tension, 42.7 dyn/cm pH 1.85). 0> Phenacetin Powder , Phenacetin Granules , Phenacetin Tablets. (From Ref. 17.). 

Dou, Y, et al., Determination of compound aminopyrine phenacetin tablets by using artificial neural networks combined with principal components analysis. Anal. Biochem., 351 174-180 (2006). 

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. 

High performance liquid chromatography is used for the separation and quantitative analysis of a wide variety of mixtures, especially those in which the components are insufficiently volatile and/or thermally stable to be separated by gas chromatography. This is illustrated by the following method which may be used for the quantitative determination of aspirin and caffeine in the common analgesic tablets, using phenacetin as internal standard where APC tablets are available the phenacetin can also be determined by this procedure. 

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... 

Figure 13 compares the dissolution rate of pure phenacetin particles with the granulated particles of the same size and with tablets prepared from these granules. These comparisons were made by using... 

A commercial analgesic tablet is stated on the packet to contain 325 mg of aspirin and 50 mg of caffeine per tablet. Two tablets + 0.0773 g of phenacetin were shaken with 10 cm3 of ethanol for 10 minutes, then 10 cm3 of 0.5 mol dm 3 ammonium formate were added and the mixture made up to 100 cm3. The tablets contain insoluble excipients, so a little of the solution was filtered before chromatography --- ... 

From the uv absorption spectra, a suitable wavelength is found for the simultaneous detection of aspirin, phenacetin and caffeine. Using phenacetin as internal standard, response factors are calculated for aspirin and caffeine and the results are used for the quantitative determination of aspirin and caffeine in an analgesic tablet. 

Procedure The drug contents of an appropriate number of tablets are directly extracted into chloroform, filtered if necessary so as to remove the insoluble tablet components, and the final concentration of chloroform solution is made in such a way so that it should contain 90 mg ml-1 of aspirin 64 mg ml 1 of phenacetin, and 134 mg ml-1 of caffeine. The IR-spectrum is now recorded in a 0.1 mm NaCl-cell between 1400-2000 cm-1. 

The nitrosation conditions of aniline and diphenylamine derivatives (paracetamol, phenacetin, mefenamic acid, and diclofenac sodium), with subsequent formation of colored products in alkaline media, were studied by Shormanov et al. [35]. Suitable procedures for quantitative determination of analytes in bulk drug substance and tablets were developed. 

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. ... 

If you wish to measure the amount of aspirin in a tablet on a routine basis which mobile-phase composition would you choose Why Which mobile phase would be suitable for monitoring phenacetin in a tablet on a routine basis Why ... 

Figure 13-4 shows an example of the phenacetin standards and APC tablet analysis on a high-efficiency column. 

FIGURE 13-1. Typical injection of APC tablet for quantitation of phenacetin. Mobile phase MeOH/H20 (4% HOAc) 35/65. Flow rate 1 mL/min. Detector UV at 254 nm, 1.0 AUFS. Sample APC tablet in 100 mL MeOH, 10 /aL. Column Bondapak Cis/Porasil B, 2 mm ID x 60 cm. (Note Actual separation will depend upon the quality of the mobile phase and column packing.)... 

For those who analyzed the APC tablet, if available, refer to Experiments for Instrumental Methods, C. N. Reilley and D. T. Sawyer, McGraw Hill, New York, 1961, pp. 185-190, and compare the spectro-photometric method for determining phenacetin in an APC tablet to the chromatographic method which you just completed. 

Dicyclomine Hydrochloride capsules Dicyclomine Hydrochloride injection Dicyclomine Hydrochloride syrup Dicyclomine Hydrochloride tablets Fused Silica 15M x 0.5 mm coated with G3(l pm) Nitrogen 160-240 20/min FID Phenacetin USP (24, pp. 549, 550 and 551)... 

Content Uniformity/Assay. The question most often asked is when NIR will be able to be used as a release test. In the earliest NIR assays, tablets and capsules were not analyzed intact. Prior to scanning, the active was extracted and scanned in a clear liquid. The first use of NIR for tablets was reported in 1968. Sherken assayed the meprobamate content in tablet mixtures and commercial preparations. Allen used NIR to analyze a three-component mix carisoprodol, phenacetin, and caffeine. The powder was extracted with chloroform and scanned in the NIR. Several other publications took advantage of the dissolve and scan approach.t ... 

Aspirin BP In fine powder form for preparation of Soluble Aspirin Tablets and Soluble Aspirin, Phenacetin and Codeine Tablets... 

Many examples of the effects of tablet excipients on dmg decompositions are reported in the pharmaceutical literature. Chemical interaction between components in solid dosage forms may lead to increased decomposition. Replacement of the phenacetin in compound codeine and ARC tablets by paracetamol in NHS formulations in Australia in the 1960s (because of the undesirable side-effects of phenacetin), led to an unexpected decreased stability of the tablets. The cause was later attributed to a transacetylation reaction between aspirin and paracetamol and also a possible direct hydrolysis of the paracetamol (Scheme 4.15). 

Figure 4.16 Development of free salicylic acid in aspirin-paracetamol-codeine and aspirin-phenacetin-codeine tablets at37X.

Allen used NIR for the quantitative determination of cari-soprodol (CAR), phenacetin (PH), and caffeine (CAF) [70]. Twenty tablets were pulverized and an aliquot dissolved in chloroform. Standard solutions of CA, PH, and CAF were scanned between 2750 and 3000 nm. Caffeine and phenacetin were determined at 2820 nm (CA) and 2910 nm (PH), with CAF determined at 3390 nm. The coefficient of variation (CV) was 1.4% or less. 

Gazdag and Nyiredy applied gas chromatography to determine ethylmorphine hydrochloride (20 mg) in tablets also containing phenacetin (300 mg) and aminophenazone (300 mn). On a SE-30 packed column the compounds were separated and could be determined, the ethylmorphine hydrochloride had a. relative standard deviation of 2.7. ... 

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. 

Dechene et al. determined acetyl salicylic acid, phenacetin, caffeine and codeine in tablets. Acetyl salicylic acid and phenacetin were separated and determined on one packed column of DS 200 on Haloport by temperature programming, 100-180°C, whereas caffeine and codeine were separated on a packed column of SE-30 (10 %) on Chromosorb W AW by temperature programming, 195-260°C. Codeine and caffeine were extracted from the powdered tablet material with chloroform after the addition of alkali, and the chloroform solution used for the gas chromatographic assay. Results obtained with the method are listed in Table 20.4. 

In order to run a series of analyses of drugs 1n pharmaceutical preparations, Fricke made use of simple extractions. Tablets containing caffeine, phenacetin and aspirin were brought into a volumetric flask, to which chloroform and a small amount of glacial acetic acid were added. After shaking for 1 h chloroform was added and an aliquot was transferred to a Celite column that was treated with 1 N NaHCO solution. After elution with chloroform, the eluate was evaporated to dryness, and the residue dissolved in methanol to about 0.3 mg/ ml of caffeine. The gas chromatography was carried out on a packed column using Dexsil 300 10 % or 17 % on Chromosorb W HP at 220°C or 222°C respectively. 

As examples the separation of aspirin, caffeine, and phenacetin (APC tablets) is accomplished by a mobile phase of methanol-acetic acid-ether-benzene (1 18 60 120) and nitroglycerine, a vasodilator, present in heart medication capsules can be separated from the other capsule materials by benzene. 

Codeine, which has only one-quarter of the toxicity of morphine, is sometimes used as a suicidal agent (2), probably because it is easy to obtain, but as the majority of such suicides are caused by tablets in which the codeine is compounded with other substances such as aspirin or phenacetin, it is difficult to say if it is really the cause of death. 

EXPERIMENT 26 ULTRAVIOLET SPECTROPHOTOMETRIC DETERMINATION OF ASPIRIN, PHENACETIN, AND CAFFEINE IN APC TABLETS USING SOLVENT EXTRACTION... 

APC tablets are a mixture of aspirin, phenacetin, and caffeine. Each of these substances has characteristic absorption in the ultraviolet region, with the principal maxima lying at 277 nm for aspirin, 275 nm for caffeine, and 250 nm for phenacetin. In the procedure, a powdered tablet is dissolved in methylene chloride, and the aspirin is separated from the phenacetin and caffeine by extracting it into aqueous sodium bicarbonate solution. The separated aspirin is back-extracted into methylene chloride by acidifying the aqueous layer and is then measured spectrophoto-metrically at 277 nm. The phenacetin and caffeine that remain in the original methylene chloride layer are determined in mixture as described in Chapter 16 (Equations 16.16 and 16.17). 

To calculate the concentrations of phenacetin and caffeine, the absorbances of the phenacetin and caffeine standards and of the methylene chloride extract of the sample must all be read at both 250 and 275 nm. Using these absorbances, calculate the percent phenacetin and caffeine in the ARC tablets and the milligrams of each per tablet. See Chapter 16 for the spectrophotometric detennination of mixtures. Use a spreadsheet similar to the one in Chapter 16 and your CD to do the mixture calculations. 

Note Component of APC tablets, also containing aspirin and caffeine. Phenacetin may reasonably be anticipated to be a carcinogen Fourth Annual Report on Carcinogens (NTP 85-002, 1985) p 165. 

Das Gupta, V. Simultaneous quantitation of acetaminophen, aspirin, caffeine, codeine phosphate, phenacetin, and salicylamide by high-pressure liquid chromatography. J.Pharm.Sci., 1980, 69,110-113 Kirchhoefer, R.D. Simultaneous determination of aspirin and sMicylic acid in bulk aspirin and in plain, buffered, and enteric-coated tablets by high-pressure liquid chromatography with UV and fluorescence detectors. J.Pharm.Sci., 1980, 69, 1188-1191... 

Sample preparation Triturate 1 tablet with a glass rod with 5 mL water, sonicate for 20 min, extract with 9 mL dichloromethane then three times with 5 mL dichloromethane, filter (paper), make up to 25 mL with dichloromethane. Remove a 500 p,L aliquot, add 200 pL 1.2 mM phenacetin in dichloromethane -I- 100 pL 0.5 mM 4-dimethylaminopyri-dine + 100 pL 100 mM N-CBZ-Phe in dichloromethane -I- 100 pL 100 mM N, N -dicy-clohexylcarbodiimide in dichloromethane, shake mechanically at 30° for 1 h, inject a 10 pL aliquot. 

Mokry, M. KUmes, J. Zahradnicek, M. HPLC anal3rsis of some sulfonamides in selected pharmaceutical formulations. Pharmazie, 1994, 49, 333—335 [tablets injections acetanilide (IS) simultaneous trimethoprim also phenacetin, phenazone, phenohenbital, phthalylsulfathiazole, sulfadimidine, sulfa-metho diazine, sulfamoxole, sulfisoxazole]... 

The quantitative analysis of a multicomponent system is illustrated by its application to the simultaneous determination, of aspirin, phenacetin and caffeine in tablets. These drug components can be determined by dissolving the sample in chloroform, with each of the components showing distinct carbonyl bands in the infrared spectrum. 

Analgesics aspirin, paracetamol, caffeine and phenacetin. Sample Anadin, APC or other proprietary analgesic tablet. TLC plates Kiesegel 10 x 5 cm 60 F254 layer thickness 0.2 mm. 

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