Pharmaceutical products analysis

R.C. Lyon, D.S. Lester, E.N. Lewis, E. Lee, L.X. Yu, E.H. Jefferson and A. S., Hussain, Near-infrared spectral imaging for quality assurance of pharmaceutical products analysis of tablets to assess powder blend homogeneity, AAPS Pharm. Sci. Tech., 3(3), 1-15 (2002). 

Lyon, R.C. Lester, D.S. Lewis, E.N. Lee, E. Yu, L.X. Jefferson, E.H. 8t Hussain, A.S., Near-Infrared Spectral Imaging for Quality Assurance of Pharmaceutical Products Analysis of Tablets to Assess Powder Blend Homogeneity AAPS PharmSciTech. 2002, 3(3), article 17, 1-15. 

The external standard calibration method is a simple but less precise method and should only be used when the sample preparation is simple and small or no instrumental variations are observed. The method is not suitable for use with complicated matrices but is often used in pharmaceutical product analysis characterized by simple matrices and easy sample preparation. To construct a standard curve, standard solutions containing known concentrations of the analyte must be prepared and a fixed volume injected into the column. The resulting areas or heights of the peaks in the chromatogram are measured and plotted versus the amount injected. Unknown samples are then prepared, injected and analyzed in exactly the same manner, and their concentrations are determined from the calibration plot. The term external standard calibration implies that the standards are analyzed in chromatographic runs that are separate from those of the unknown sample. 

The suggested tolerances for the validation parameters in the FDA recommendations for bioanalytical methods [16] are rather wide, with C.V. values < 15%. For pharmaceutical product analysis the requirements are tighter with C.V. values < 2% [82], This is possible, since in the latter case the matrix is typically much simpler and the analyte concentration can be chosen freely, so that extremely low/high concentrations can be avoided. 

The tolerances (C.V.-values) of the validation terms can be much narrower in this work 10% is suggested. This value is between the accepted tolerances for bioanalytical methods and those for pharmaceutical product analysis. 

Applications of SFA/LC include the determination of drugs in blood serum, pharmaceutical product analysis, and the determination of vitamin A in milk. 

A study was conducted to measure the concentration of D-fenfluramine HCl (desired product) and L-fenfluramine HCl (enantiomeric impurity) in the final pharmaceutical product, in the possible presence of its isomeric variants (57). Sensitivity, stabiUty, and specificity were enhanced by derivatizing the analyte with 3,5-dinitrophenylisocyanate using a Pirkle chiral recognition approach. Analysis of the caUbration curve data and quaUty assurance samples showed an overall assay precision of 1.78 and 2.52%, for D-fenfluramine HCl and L-fenfluramine, with an overall intra-assay precision of 4.75 and 3.67%, respectively. The minimum quantitation limit was 50 ng/mL, having a minimum signal-to-noise ratio of 10, with relative standard deviations of 2.39 and 3.62% for D-fenfluramine and L-fenfluramine. 

This procedure was tested in the analysis of pharmaceutical products Poltava s bishofite (series Elite and Profi ) and a brine of bischofite with rusty precipitate. The data bear out the sufficient accuracy and reproducibility of the proposed procedure which allows to perform the determination magnesium, iron, copper and zinc ions at concentrations above 10 M. It was found that the content of Mg ion in the studied brine decreases in comparison with Poltava s bishofite . The Fe, Cu and Zn ions were not detected in the brine. 

As a matter of fact, the main advantage in comparison with HPLC is the reduction of solvent consumption, which is limited to the organic modifiers, and that will be nonexistent when no modifier is used. Usually, one of the drawbacks of HPLC applied at large scale is that the product must be recovered from dilute solution and the solvent recycled in order to make the process less expensive. In that sense, SFC can be advantageous because it requires fewer manipulations of the sample after the chromatographic process. This facilitates recovery of the products after the separation. Although SFC is usually superior to HPLC with respect to enantioselectivity, efficiency and time of analysis [136], its use is limited to compounds which are soluble in nonpolar solvents (carbon dioxide, CO,). This represents a major drawback, as many of the chemical and pharmaceutical products of interest are relatively polar. 

Legal requirements for pharmaceutical product assessment and registration specify how pharmaceutical production should be carried out, and lay down requirements concerning packaging, information to be provided by labels and inserts, methods of analysis, etc. 

How does green chemistry now relate to pharmaceuticals production A special challenge for manufacturing of pharmaceuticals is the complexity of the molecules, which requires many synthesis steps. For example, an analysis of 128 drug candidates from three major pharma companies showed that, on average, eight steps are required for the synthesis of active... 

Method The authors use information on all non-hospital sales of pharmaceutical products in 1992 in a sample of countries consisting of the USA, Canada, Germany, France, Italy, Japan and the UK. The database was provided by Intercontinental Medical Systems (IMS). The empirical analysis is based on the calculation of the Paasche and Laspeyres price indexes and the ratio between them. The descriptive analysis is completed with the econometric analysis (quasi-hedonic model) of the determining factors of the variation in the relative prices of each active ingredient in each country taking the USA as the point of comparison. 

The information in the Prescription Cost Analysis System and the Base de Datos de Especialidades Farmaceuticas (Pharmaceutical Product Database) is compiled according to accounting criteria. We processed the information and created two structured databases in order to obtain the statistics that will show us the competition and the structure of the pharmaceutical markets of each of the countries studied. 

Selection of a suitable analytical method can be made once the reason for carrying out the analysis is well understood. Analytical methods may be (a) qualitative or (b) quantitative or semi-quantitative. The former usually pose few problems if only an indication is required as to whether a particular analyte is present or not - certainly not how much with a value having a small uncertainty. If a negative result is required (i.e. confirmation of absence from the product), then one has only to worry about the limit of detection of the test used. Many tests to confirm the absence of impurities in pharmaceutical products fall into this category. Equally, rapid tests for positive confirmation are often made on unknown substances. These may subsequently be confirmed by other, quantitative tests. Quantitative methods are used in a variety of situations and a variety of different methods can be employed. What you must always remember is that the method used must be fit for the purpose. 

Koneru, P., "To Promote the Progress of Useful Articles An Analysis of the Current Utility Standards of Pharmaceutical Products and Biotechnological Research Tools," IDEA J. L. Technol, 38, 625-671 (1998). 

In pharmaceutical drug analysis a host of organic pharmaceutical substances are invariably converted quantitatively to their corresponding derivatives by virtue of interactions with certain functional entities, namely aldehyde, ketone, amino, carboxyl, phenolic, hydroxyl etc. However, in some cases it may be feasible to obtain uniform substitution products of organic pharmaceutical substances quantitatively, for instance tetraido derivative of phenolphthalein is obtained from the phenolphthalein tablets. It is important to mention here that the number of organic pharmaceutical substances which may be analysed by this method is limited because of two vital reasons, they are ... 

One of the most difficult and frustrating problems ever encountered in the domain of pharmaceutical analysis is that of the simultaneous separation, identification and above all the quantitation of more than one compound from a complex mixture in a pharmaceutical product. 

The textbook on Pharmaceutical Drug Analysis would enormously serve the undergraduates, postgraduates, researchers, analytical chemists working in the Quality Assurance Laboratories, new drug development, production and control, teaching, or regulatory authorities. 

There has been significant advancement in the applications of NMR to the development of small-molecule pharmaceutical products. For example, advances in NMR automation (e.g., flow-injection analysis) and directly coupled methods (e.g., LC-MS-NMR analysis) have made analysis and characterization of small-molecule drugs much easier.23 25 These improvements have helped chemists to develop and characterize small-molecule combinatorial libraries and to screen for active compounds.4 6 It is likely some of these techniques can also be used in biopharmaceutical product development. 

Near infrared spectroscopy (NIRS), a technique based on absorption and reflectance of monochromatographic radiation by samples over a wavelength range of 400-2500 run, has been successfully applied for food composition analysis, for food quality assessment, and in pharmaceutical production control. NIRS can be used to differentiate various samples via pattern recognitions. The technique is fast and nondestructive method that does not require sample preparation and is very simple to use compared too many other analytical methods such as HPLC. The drawback of NIRS, however, is that the instrument has to be calibrated using a set of samples typically 20-50 with known analyte concentrations obtained by suitable reference methods such as FIPLC in order to be used for quantitative analyses. Simultaneous quantification of the... 

The hyphenation of CE and NMR combines a powerful separation technique with an information-rich detection method. Although compared with LC-NMR, CE-NMR is still in its infancy it has the potential to impact a variety of applications in pharmaceutical, food chemistry, forensics, environmental, and natural products analysis because of the high information content and low sample requirements of this method [82-84]. In addition to standard capillary electrophoresis separations, two CE variants have become increasingly important in CE-NMR, capillary electrochromatography and capillary isotachophoresis, both of which will be described later in this section. 

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