Error analysis volumetric

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... 

The nonideal chemical or physical behavior of the reagents and reactions on which an analysis is based often introduces systematic method errors. Such sources of nonideality include the slowness of some reactions, the incompleteness of others, the instability of some species, the nonspecificity of most reagents, and the possible occurrence of side reactions that interfere with the measurement process. For example, a common method error in volumetric analysis results from the small excess of reagent required to cause an indicator to undergo the color change that signals completion of the reaction. The accuracy of such an analysis is thus limited by the very phenomenon that makes the titration possible. 

The design and operation of a highly accurate large flow cryogenic calibration stand has proven quite successful. The test system has been used to calibrate flowmeters using liquid oxygen, liquid nitrogen and distilled water. The maximum absolute error of the test system as obtained from the error analysis is 0.28 for the calibration of volumetric-type flowmeters, and 0.17 for the calibration of mass type flowmeters. 

In this section, potential errors for the volumetric technique are discussed. Also, relevant are the errors analyzed under General Error Analysis section. 

GENERAL ERROR ANALYSIS - COMMON TO BOTH VOLUMETRIC AND GRAVIMETRIC... 

Kluitenberg, G., Ham, J. Bristow, K (1993). Error analysis of the heat pulse method for measuring soil volumetric heat-capadty. Soil Science Society of America Journal, Vol. 57, No.6, pp.1444-1451. 

An estimate of compound random errors is obtained from the square root of the sum of the squares of the RSDs attributed to each component or operation in the analysis. If the analysis of paracetamol described in Box 1.3 is considered then, assuming the items of glassware are used correctly. Assuming the items of glassware are used correctly the errors involved in the dilution steps can be simply estimated from the tolerances given for the pipette and volumetric flasks. The British Standards Institution (BS) tolerances for the grade A glassware used in the assay are as follows ... 

The volume of reagent (titrant) required for stoichiometric reaction of analyte is measured in volumetric analysis. The stoichiometric point of the reaction is called the equivalence point. What we measure by an abrupt change in a physical property (such as the color of an indicator or the potential of an electrode) is the end point. The difference between the end point and the equivalence point is a titration error. This error can be reduced by subtracting results of a blank titration, in which the same procedure is carried out in the absence of analyte, or by standardizing the titrant. using the same reaction and a similar volume as that used for analyte. 

Conway, E. J. Microdiffusion Analysis and Volumetric Error, 4. Edition. London Crosby Lockwood Son Ltd. 1957. 

In the example above, the sample preparation contributed 75% of the error. When multiple steps such as those shown in Figure 1.2 are involved, the uncertainty is compounded. A simple dilution example presented in Figure 1.5 illustrates this point. A 1000-fold dilution can be performed in one step 1 mL to 1000 mL. It can also be performed in three steps of 1 10 dilutions each. In the one-step dilution, the uncertainty is from the uncertainty in the volume of the pipette and the flask. In the three-step dilution, three pipettes and three flasks are involved, so the volumetric uncertainty is compounded that many times. A rigorous analysis showed [3] that the uncertainty in the one-step dilution was half of what was expected in the three-step process. 

Sample solutions are prepared in volumetric flasks using distilled water at a temperature of 18 °C. The volumetric flask has been calibrated at a temperature of 20 °C. This will lead to a small systematic error in the results of analysis of the sample solutions because the volume will be different from the stated value. 

Errors due to approximations in the experimental data analysis. Several potential errors were introduced when the measured volumetric flow rates were converted to molar flow rates. Volumetric gas flow rates were converted using the idc il gas equation of state, which is approximate, and the volumetric liquid flow rate was converted using a tabulated density that may not have been measured at the system temperature. Also, the fact that a physical property value has been published is no guarantee that it is correct. 

Sources of error can be introduced in each conversion from volume to moles and back to weight, although for simple examples such as the one above it does not really matter which method of calculation is employed as long as the correct answer for the purity of citric acid is obtained. However, for more complicated calculations, involving the use of back and blank titrations, this author believes that factors and equivalents simplify volumetric analysis and they will be used for that reason (rather than any reason of dogma) in the remainder of this book. 

M Color blindness is a good example of a limitation that could cause a personal error in a volumetric analysis. A famous color-blind analytical chemist enlisted his wife to come to the laboratory to help him detect color changes at end points of titrations. 

Most of the methods in use in clinical chemistry laboratories involve colorimetric analysis in fewer instances volumetric or gravimetric procedures are still retained. It is not the purpose of this review to enter into a discussion of the errors inherent in colorimetric, volumetric, and gravimetric analysis as such for a treatment of this subject the reader is referred to standard works on chemical analysis (e.g., V3). Instead, the review will be confined to those sources of error that are particularly likely to affect the work of a clinical laboratory. These errors arise mainly from the need to perform many analyses on large numbers of samples with a variable degree of urgency, and from the fact that most of these analyses have to be conducted on plasma or semm, which are viscous protein-rich fluids available only in restricted quantities (M12). 

The accuracy of the liquid chromatographic analysis of the generated solutions is limited by the uncertainties involved with the calibration of the sample loop, with the preparation of standard acetonitrile solutions of the PAHs, and with the volumetric measurement of the amount of saturated solution sampled for a given analysis. The random errors associated with each of these processes have been estimated to be less than 1.2%, 0.1%, and 1.0%, respectively. A detailed explanation of how each of these estimates was made is presented elsewhere (39). Quadratic addition of these random errors yields a minimum uncertainty of 1.6% for the quantitative analysis of the generated saturated solutions and hence a potential accuracy of greater than 98% for the method. 

Conway Microdiffusion Analysis and Volumetric Error 4th Ed. Crosby Lockwood, London, 1957... 

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