Errors in pharmaceutical analysis

This chapter has been divided into two different portions, namely (a) Errors in Pharmaceutical Analysis, and (b) Statistical Validation, which will be discussed individually in the following sections ... 

Part—I has three chapters that exclusively deal with General Aspects of pharmaceutical analysis. Chapter 1 focuses on the pharmaceutical chemicals and their respective purity and management. Critical information with regard to description of the finished product, sampling procedures, bioavailability, identification tests, physical constants and miscellaneous characteristics, such as ash values, loss on drying, clarity and color of solution, specific tests, limit tests of metallic and non-metallic impurities, limits of moisture content, volatile and non-volatile matter and lastly residue on ignition have also been dealt with. Each section provides adequate procedural details supported by ample typical examples from the Official Compendia. Chapter 2 embraces the theory and technique of quantitative analysis with specific emphasis on volumetric analysis, volumetric apparatus, their specifications, standardization and utility. It also includes biomedical analytical chemistry, colorimetric assays, theory and assay of biochemicals, such as urea, bilirubin, cholesterol and enzymatic assays, such as alkaline phosphatase, lactate dehydrogenase, salient features of radioimmunoassay and automated methods of chemical analysis. Chapter 3 provides special emphasis on errors in pharmaceutical analysis and their statistical validation. The first aspect is related to errors in pharmaceutical analysis and embodies classification of errors, accuracy, precision and makes... 

What are the two major types of errors invariably encountered in pharmaceutical analysis Explain with suitable examples. 

Meanwhile, these chemicals—like chemical agents encountered at work or in hobbies or as pollutants in air, water, soil, or food—can also cause harm. Sometimes the known mechanisms of action permit us to predict the nature of toxicity to be expected. A meta-analysis of prospective studies from U.S. hospitals indicates that 6.7% of in-patients have serious adverse drug reactions 0.3% have fatal reactions (Lazarou et al., 1998). In fact, estimates of 40,000 to 100,000 deaths per year attributed to errors in medical care, primarily due to adverse reactions to pharmaceuticals, make this phenomenon a major cause of death in the United States (Meyer, 2000). A tremendous... 

The famous adage— to err is human to forgive divine,—literally means that it is natural for people to make mistakes. However, errors in analytical chemistry or more precisely in pharmaceutical drug analysis are normally of three types, namely ... 

Panderi and Parissi-Poulou developed a microbore liquid chromatographic method for the simultaneous determination of benazepril hydrochloride and hydrochlorothiazide in pharmaceutical dosage forms [30]. The use of a BDS C-18 microbore analytical column was found to result in substantial reduction in solvent consumption and in increased sensitivity. The mobile phase consisted of a mixture of 25 mM sodium dihydrogen phosphate buffer (pH 4.8) and acetonitrile (11 9 v/v), pumped at a flow rate of 0.4 mL/min. Detection was effected at 250 nm using an ultraviolet absorbance detector. The intra- and inter-day relative standard deviation values were less than 1.25% (n = 5), while the relative percentage error was less than 0.9% (n = 5). The detection limits obtained according to the IUPAC definition were 0.88 and 0.58 pg/mL for benazepril hydrochloride and hydrochlorothiazide, respectively. The method was applied to the quality control of commercial tablets and content uniformity test, and proved to be suitable for rapid and reliable analysis. 

Poor values for linearity are usually the result when only production samples are used for development of quantitative calibrations. The low R values are a result of the narrow range of active concentrations due to the quality that is inherent in pharmaceutical processes. A typical pharmaceutical process gives samples that vary little from the nominal value. Typical ranges for tablet assays fall within a range of 97 to 102% of label claim. This 5% range, coupled with errors in the HPLC analysis, lead to a poor correlation line. In HPLC or UV/VIS spectroscopic methods, an R value approaching unity is common the U.S.P. recommends a value no lower than 0.995. A typical NIR linearity, based solely on actual production samples, is often closer to 0.8 than 1.0 due primarily to the narrow range. 

Sulfacetamide, A benzoyl sulfanilamide and sulfathiazole have been determined in pharmaceutical preparations by measuring absorbance of the mixture in 0.1 N hydrochloric acid at 220,235 and 280 nm respectively (42). Madsen et al. (43,44) have performed computer analysis of the multicomponent UV spectra of sulfonamides. The errors in concentration determined from the spectra between 240 and 272 nm are lower when the spectra are analysed by a linear-squares method considering the data over the whole wavelength range compared with the determination using the data at a single wave length. The method has been applied to the assay of sulfacetamide sodium eye-drops. 

Sample preparation of pharmaceutical products is an important step in the analysis methodology and must be carefully carried out to avoid contamination, loss of metal(s) or addition of interferences that could result in errors in the measurements. Modem versions of the international pharmacopoeias contain methods involving atomic emission methods, and some replace tedious titration, spectrophotometer or gravimetric methods. 

More sophisticated approaches to predict the extent of oral absorption of drugs use mathematical models based on the known physiology and utilizing simple physicochemical measurements as input. The GastroPlus [4] program is a commercial tool that utilizes an advanced compartmental and transit model, based on the work of Amidon and Yu [5], and allows what-if questions to be posed to enable pharmaceutical optimization (see Chapter 17). For instance, the impact of morphology, formulation, and/or particle size changes, and sensitivity analysis to include errors in parameters on the prediction, can be considered. 

Various quality control checks are define in the USEPA methods dealing with gas chromatography to control errors and ensure the methods are being run in the proper manner. In environmental analysis, nobody knows the correct answer unlike in some industries (e.g., food and pharmaceutical) where a target value is confirmed or denied. Environmenfal data can be and is often compared and, therefore it is important that methods be run in a controlled manner. Results are often far less than quantitative. Precision and accuracy are monitored, but in ways that are different from those in other fields of analytical chemistry. These concepts will be addressed below. 

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