Paracetamol analytical method

How analytical methods deal with interferences is one of the more ad hoc aspects of method validation. There is a variety of approaches to studying interference, from adding arbitrary amounts of a single interferent in the absence of the analyte to establish the response of the instrument to that species, to multivariate methods in which several interferents are added in a statistical protocol to reveal both main and interaction effects. The first question that needs to be answered is to what extent interferences are expected and how likely they are to affect the measurement. In testing blood for glucose by an enzyme electrode, other electroactive species that may be present are ascorbic acid (vitamin C), uric acid, and paracetamol (if this drug has been taken). However, electroactive metals (e.g., copper and silver) are unlikely to be present in blood in great quantities. Potentiometric membrane electrode sensors (ion selective electrodes), of which the pH electrode is the... 

In various recent publications, the analytical method was given equal time with the validation scheme. Forbes et al. [22] presented a trace analysis method for residual isopropanol in loracarbef using NIR. The validation implications for trace analyses were examined in the paper. Trafford et al. [23] used reflectance NIR to determine the active in paracetamol tablets. Again, validation issues were discussed. 

Bindschaedler and Gurny [12] published an adaptation of the simplex technique to a TI-59 calculator and applied it successfully to a direct compression tablet of acetaminophen (paracetamol). Janeczek [13] applied the approach to a liquid system (a pharmaceutical solution) and was able to optimize physical stability. In a later article, again related to analytical techniques, Deming points out that when complete knowledge of the response is not initially available, the simplex method is probably the most appropriate type [14]. Although not presented here, there are sets of rules for the selection of the sequential vertices in the procedure, and the reader planning to carry out this type of procedure should consult appropriate references. 

Parimoo et al. [18] established a UV spectrophotometric method for the simultaneous determination of mefenamic acid and paracetamol in combination preparations. The determination was carried out in two different solvents, namely methanol and 0.1 N NaOH. The wavelength maximum for mefenamic acid was found at 284 nm, and 248 nm for paracetamol. The wavelength maximum for mefenamic acid in NaOH was found at 219 nm, and 256 nm for paracetamol. There were no interferences in the analyte estimations. 

Ahrer et al. [69] developed methods for the determination of drug residues in water based on the combination of liquid chromatography (LC) or capillary electrophoresis (CE) with mass spectrometry (MS). A 2 mM ammonium acetate at pH 5.5 and a methanol gradient was used for the HPLC-MS allowing the separation of a number of drugs such as paracetamol, clofibric acid, penicillin V, naproxen, bezafibrate, carba-mazepin, diclofenac, ibuprofen, and mefenamic acid. Apart from the analytical separation technique, water samples have to be pretreated in order to get rid of the matrix components and to enrich the analytes the usual way to accomplish this aim is to perform a solid-phase extraction... 

This manifold has been used for the USALLE of paracetamol from suppositories [17]. Hydrolysis of the analyte prior to reaction with o-cresol in the alkaline extractant medium was also favoured by US (the entire sample plug was irradiated in EC). Hydrolysis and formation of the reaction product displaced the extraction equilibrium, thus favouring extraction into the aqueous phase. The influence of the variables related to the dynamic manifold (namely, flow rate and sample volume), chemical variables (namely, NaOH and o-cresol concentrations) and temperature was studied using the univariate method on account of their independence on the other hand, those related to US (namely, probe position, radiation amplitude and pulse duration) were the subject of a multivariate study in which the latter two exhibited an insignificant but positive effect. Positioning the probe closest to the extraction coil was found to maximize extraction efficiency. The positive effect of US on extraction and analyte hydrolysis provides the overall enhancement shown in Fig. 6.4A, which shows the results obtained in the presence and absence of US. The time required for the development of the method was significantly shorter than that required by the United States Pharmacopoeia (USP) method. In addition, the latter produces emulsions that need about 30 min for phase separation after extraction. 

Although the earliest examples of the use of US as a substitute for phase transfer catalysts in organic addition reactions were reported more than two decades ago and a number of such reactions have since been improved as a result [1-7], the sole analytical application exploiting this potential is a method for the determination of paracetamol where the drug is derivatized by hydrolysis to p-aminophenol, which reacts with o-cresol in an alkaline medium to form the Indophenol Blue dye, according to the following reaction ... 

Not all aspects of a full validation protocol are important for particular uses of some methods. For example, limits of detection or determination are not an issue for the analysis of the active in a 500 mg paracetamol tablet, but for trace impurities it is, of course, necessary to demonstrate these limits. However, in the documentation of a method validation it is useful to include each heading and at least give reasons for asserting that, as in the example above with limit of detection, one or more headings are manifestly satisfied. Table 2 gives some examples of parameters that must be considered particularly carefully for different analytical requirements. It is stressed, however, that these are the parameters that address the particular requirements tabulated, and that other aspects might need to be validated to achieve a complete method validation. 

Generally, AA is determined individually, and only about a 10% of the published methods determine AA simultaneously with other analytes such as uric acid, glucose, fructose, dopamine, iodate, bromate, hypochlorite, thiourea, glutathione, hydrogen peroxide, acetylsalicylic acid, kojic acid, ascorbyl glucoside, paracetamol, cysteine, and other water soluble vitamins (thiamine [vitamin Bj], folic acid [vitamin B12], niacin [vitamin B3], riboflavin [vitamin B2], and pyridoxine [vitamin B ]). 

However, the small injection volume available to CE (a few nl) means that high sensitivity can only be achieved if concentrations of the analyte in the sample are high. Nevertheless, some results have been reported using CE-NMR and the method has been applied to the identification of paracetamol metabolites in human urine. Finally the application of capillary electrochromatography (CEC) directly coupled to NMR has been explored using the same paracetamol metabolite samples. 

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