Page 1 :
2., ERRORS, INTRODUCTION, In pharmaceutical analysis, the aim if an analyst that is performing analytical, operation/experiment in analytical laboratory must be that he or she must obtain a true result, by performing an analytical procedure correctly as required. But in reality, an analyst which, have knowledge about the various aspects of analytical operations knows very well that the true, or theoretical value of result is very rare and he/she should only try to get his/her results close, to the true value. How much close is the result to the true value depends upon the knowledge, of analyst towards the chemistry or principle of operation, possible interferences in operation, i.e. from other ions, elements and compounds as well as hands-on experience about the, statistical distribution of values., ERROR, The term error refers to the difference between the measured and true value in the results of, any analytical operation., However, it is not possible to eliminate error from any measurement, even the person, performing the operation is expert, performing operation in best conditions and performing on, best quality instrument. One should only made attempts to minimize errors and get results, which are close to the true value at best possible., To check the error analyst must know the true value of particular experiment's results but term, "true value" is never ever known in reality. Analyst have to make use of a standard value instead, of true value which can be obtained by two methods:-, 1. Absolute method:-The sample which is to be analyzed can be synthesized/prepared using, known quantities of constituents in known conditions to get a primary standard. In this primary, standard the true values of constituents are known. Then it is analyzed by some suitable method, and value obtained is recorded and considered as standard value. Now the sample is analyzed, by same method in same conditions and observed value is recorded. From above two values, error can be calculated for that method., 2. Comparative method:-Sorpetimes it is not possible to synthesize/prepare a sample under, analysis. In that case, the analytical data provided by some standard agency is regarded as, absolutely true. From that the error can be calculated., Scanned with CamScanner, 20
Page 2 :
ERRORS, 21, SOURCES OF ERRORS, Errors in the results in an analysis can be resulted from various sources. Some major sources of, errors in pharmaceutical analysis are described here under., 1. Human source:- The qualification and experience of an analyst performing the analysis has, major impact on error in results. If an experiment is performed by inexperienced person the, chances of error are more as compared to same experiment performed by the experienced, analyst., 2. Instrumental, apparatus and glassware:- If the instrument, glassware as well as apparatus, used in analysis is of low quality and uncallibrated the chances of error are increased at, significant extent., 3. Experimental conditions:- If the analysis is carried out in the conditions which are, unfavourable for particular experiment or analysis the desirable result will not obtained., 4. Constituents used in analysis:- If various constituents like standard, solvents, reagents etc, used in analysis are not of desired quality and purity the results will be obtained with errors., 5. Procedure:- If the analytical procedure used in analysis is not validated and if validated but, not followed carefully the errors in the results will obtained., TYPES OF ERRORS, Errors occurs in analysis can be majorly classified into two types:-, 1. Systemic errors:- Systemic errors is also known as determinate errors. These are the errors, whose source or cause as well as magnitude is known and can be avoided or minimized by, following proper procedure carefully and taking necessary precautions. Systemic errors can, be classified as follows:-, a. Personal errors:-For these errors the person carrying operation or experiment is responsibly., These errors occurs when the procedure is not properly followed or done carefully. These, errors are common when analyst not personally doing operation but connected to the, procedure as observer. Some of the examples of personal errors are:-, i. Person carrying titration cannot able to detect endpoint by colour change clearly and, always add some more amount of titrant that actually required which result in positive, error i.e. measured value is always bit more than standard value., ii., Person is not washing precipitate properly in gravimetric determinations that result's, error in final result., if. Person 'performing assay has not free hand in making dilutions and add more or less, solvent in dilution preparations that directly give error in results., iv. Person carrying titrations is unable to read burette properly and always note incorrect, values that also cause error in results., b. Instrumental errors:- Instrumental errors are seen when the instrument used in the, operation doesn't give accurate measurement which it needed to be give. These are due to, Scanned with CamScanner
Page 3 :
PV A TEXT BOOK OF PHARMACEUTICAL ANALYSIS-I, 22, use of uncalibrated or improperly calibrated glassware's like pipette, burette etc and, instruments like spectrometers, pH meters, potentiometers etc., c. Reagent errors:- Reagent errors are due to the reagents used in analysis. These errors are, seen when contaminated reagents are employed in analysis or the reagents attacks on the, apparatus or glassware and introduce impurities in analyte sample under analysis., d. Method errors:- These errors are not easy to detect which are usually occurs when the, analytical method is not performed properly or is unsuitable for particular analysis. Some, examples of method errors are:-, Calculations in chemical reactions are made on the completion of reaction at specific, time as per procedure. But sometimes due to slight variability in experimental conditions, the reaction is not completed i.e. only 97% completed and calculations are made. This, results error in measurement., 1., ii. In U.V. spectrophotometric analysis, the use of different absorption maxima from that of, specific for the analyte cause poor absorption and cause error in results., iii. When pH of solvent is not adjusted properly it also give inaccurate response in HPLC and, give error in final results., iv. In gravimetric analysis, another substance present in the sample is also get precipitated, along with desired substance which give error in results., e. Additive errors:- These errors are independent of the amount of substances present in the, sample. For example, Loss in the weight of crucible during the incineration of precipitate, gives error in final results., f. Proportional error:- The magnitude of proportional error depends upon the amount of, sample. Proportional error is usually due to the materials that interferes the analytical, procedure. For example, use of impure NaOH in titration of HCI give error in results and, concentration of NaOH is proportional to the error in results., g. Constant error:- The constant error is independent of the magnitude of measured amount, but become less significant as the magnitude increased. For example, In titrations addition of, 0.1 ml more titrant in 10 ml titrand to see colour change clearly at the endpoint gives error of, 0.1ml. Similarly for 20 ml titrand 0.1 ml more titrant is added it also give same 0.1 ml error, even on double the size of sample. Therefore as the amount of titrand increases the, significance of constant error decreases., 2. Random error:- Random error is also known as indeterminate error. The cause of random, error is usually not known therefore cannot eliminated by careful working or taking, precautions during analysis. For example a person performing titration by same method in, same conditions for same sample, the results are not identical. The error observed in that, condition is called random error., Scanned with CamScanner
Page 4 :
ERRORS, 23, METHODS OF MINIMIZNG ERRORS, As we know the error is an indifferentiate part of any analytical operation. Analyst try his best to, minimize the error as much as possible. Errors can be minimized by applying following methods, during analysis:-, 1. Proper callibration of instruments, apparatus and applying corretions:- By callibration of, instruments like U.V. spetrophotometer, pH meter, potentiometer etc and glasswares like, burette, measuring cylinder etc before performing analysis one can eliminate errors to very, much extent. Errors can also be minimized by applying necessary corrections if the source of, error is known., 2. By running control determination:- By running a control determination parallerly to the, sample by taking standard under same experimental conditions the error can be reduced at, very possible extent. However, a standard should contain same weight of the constituent, present in unknown sample. The weight of the constituent of unknown sample can be, calculated as follows., result for standard, weight of constituent in standard, result for unknown, X, Where,, x = weight of constituent in unknown sample., 3. By running blank determination:- Blank determination is the determination under same, experimental conditions which are used for sample analysis but in this case the sample is, excluded. The aim of blank determination is know the effect of impurities introduced by, reagents on results. From the readings obtained from blank determination one can, eliminate the error at very much extent., 4. By comparing results of independent methods:- In that case, the analysis of same sample, by totally different methods is performed and the results obtained from both methods are, compared. If they are identical than they are considered as reliable. For example:-, Determination of strength of HCI solution is performed by titration with standard NaOH and, also by precipitation titration method with Analytical as AgCl2 and results obtained from, both methods are compared. Another example is of hardness of water, in this case the, concentrations of magnesium and calcium is determined by both atomic absorption, spectroscopy and EDTA titrations and results are compared., 5. By using standard addition:- In this method, small amount of standard of constituent, present in sample is added and sample is analyzed for the total amount of constituent, present. The difference in the results from sample with and without added standard is, calculated. Satisfactory recovery gives the confidence of accuracy of result., 6. By using internal standard:- In this method, the fixed amount of a reference material is, added to a series of known concentrations of material to be analyzed. The ratios of values, obtained for the internal standard and series of known concentrations are plotted against, concentration on a graph which gives a straight line. Same amount of internal standard is, Scanned with CamScanner
Page 5 :
PV A TEXT BOOK OF PHARMACEUTICAL ANALYSIS-I, then added to the unknown concentration and determined by same method and ratie, obtained is plotted on graph to calculate exact concentration., ACCURACY, The term "accuracy" refers to the concordance between the measured and true value or in, other word it refers that how much close the measured value is to the true value. It also reffers, as "correctness of measurement". In relation to error accuracy is inversely proportional to it i.e., more the accuracy less will be the error or vice-versa., 1, Accuracy, %3D, error, For analytical method, accuracy can be calculated by two methods which are:-, 1. Absolute method:- In this method, the analysis is carried out by a specific method on the, standard sample of high purity which can be obtained from a standard source or synthesized by, analyst in laboratory with rigorous purification and values of results are noted down. Using, same method the analysis of same sample is carried out but this time possible interferences are, added to the sample and values of results are noted down. From the values obtained from, standard and standard sample with added interferences the accuracy of the method in the, absence and presence of interferences can be determined., 2. Comparative method:- Comparative method is useful when primary standard can be, unavailable and impossible to prepare in laboratory by analyst i.e. mineral, ore, alloy etc. In that, case results from a standard source with same method is correlated to get confidence of, accuracy. Sometimes secondary standards are used for analysis., Another approach include two fundamentally different methods are employed in analysis of, same sample and their results are correlated for accuracy determination., PRECISION, Precision refers to the degree of closeness between the several measurement of same quantity, of sample by same method., Precision and accuracy are correlated to each other, Accuracy represents correctness of, measurements while precision represents reproducibility. Precision always represent accuracy, but higher degree of accuracy doesn't necessarily represent that the method is precise., For example:- Two analysts performed analysis on a sample that contain 70.10% ± 0.04% of a, constituent. The results obtained by them are as follows:-, Results of analyst A are 70.07, 70.18, 70.14, 70.08 and average value is 70.12, Scanned with CamScanner, 24
