Pharmaceuticals quantitative aspects

The most useful pharmacokinetic variable for describing the quantitative aspects of all processes influencing the absorption (fa) and first-pass metabolism and excretion (Eg and Eh) in the gut and liver is the absolute bioavailability (F) [40]. This pharmacokinetic parameter is used to illustrate the fraction of the dose that reaches the systemic circulation, and relate it to pharmacological and safety effects for oral pharmaceutical products in various clinical situations. The bioavailability is dependent on three major factors the fraction dose absorbed (fa) and the first-pass extraction of the drug in the gut wall (EG) and/or the liver (EH) (Eq. (1)) [2-4, 15, 35] ... 

Altria, K. D. (1993). Quantitative aspects of the application of capillary electrophoresis to the analysis of pharmaceuticals and drug-related impurities. /. Chromatogr. 646, 245—257. 

In the following pages, an attempt will be made to describe many of the properties of the solid state that come into play and need to be considered when formulating low-dose pharmaceuticals. The solid forms may be broadly classified as crystalline and amorphous and then describe the solid-state techniques used in their characterization. Many of the quantitative aspects and their respective advantages and disadvantages will be described. Finally, a few approaches will be described that may be used to investigate the effect of formulation on the low-dose active ingredient in the tablet. 

Most of the functions of a modern pharmaceutical company developed as the industry itself matured, and they often started out as empirical rules of thumb and folklore, known only to a few specialists. These various facets of drug discovery gradually became established as specialist disciplines in their own right. As with most scienees, hand in hand with this development eame the application of quantitative approaches. By quanitative approaehes , we mean numerical analysis to enable robust predictions to be made. This book aims to show how these different parts of the drug discovery process have developed, with partieular emphasis on quantitative aspects, and how they might progress... 

NMR-spectroscopy has been extensively employed for the identification testing as well as quantitative analysis of pharmaceutical substances. These two aspects shall be discussed in the sections that follow ... 

The following four aspects of chromatography shall be discussed in Part V of this book in addition to applications of these chromatographic techniques exclusively to quantitative analyses of pharmaceutical substances ... 

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 present chapter will review instrumental aspects for successful coupling of CE with MS, regarding interfaces, ionization sources, and analyzers. Practical considerations concerning different CE modes such as CZE, NACE, MEKC, and CEC coupled with MS will also be discussed and illustrated with a focus on recent pharmaceutical applications. Additionally, quantitative CE-MS will be presented and various methodologies used to achieve sensitive and repeatable analysis will be discussed. Finally, the final section of this chapter will give an overview on new devices (i.e., microchips), hyphenated to MS, in terms of fabrication methods, microchip designs, MS interfacing, and applications. 

Sleno, L., and Volmer, D. A. (2005). Some fundamental and technical aspects of the quantitative analysis of pharmaceutical drugs by matrix-assisted laser desorption/ionization mass spectrometry. Rapid Commun. Mass Spectrom. 19 1928-1936. 

Cartwright AC, Matthews BR (eds) (1994) International Pharmaceutical Product Registration, Aspects of Quality, Safety and Efficacy. Taylor Francis, London, pp 58Iff Dyer A (1980) Liquid Scintillation Counting Practice. Heyden Son Ltd, London Philadelphia Krull I, Swartz M (1998) Determining limits of detection and quantitation. LCGC Oktober 1998... 

Quality control, pharmaceutical product identity checks, and quantification are important fields in the broad application of the different spectroscopic methods. There are many spectroscopic aspects, e.g., concerning sample preparation, influences from different accessories, and possibly spectrometer effects, which certainly influences quantitative measurements. The latter problems could be solved using calibration transfer between different spectrometer types, for example, a scanning and an FT-near-IR spectrometer. 

The transfer of phosphorus from the terrestrial biomass to soil as dead organic matter has been estimated to be 136.4 TgP y 133.3 Tg P y is derived from plants and 3.1 Tg P y from animal material (Pierrou, 1976). The uptake of phosphorus by plemts from soil was calculated by Bazilevich (1974) to be 178TgPy while Stumm (1973) estimated it to be 236.8 Tg P y including that of the freshwater ecosystems. The terrestrial biota has been calculated to absorb 0.065 Tg P y from aquatic ecosystems and 0.063 Tg P y from industrially made foodstuffs and pharmaceutical products (Pierrou, 1976). An important aspect on which quantitative data are not yet available is the bacterial cycling of phosphorus within soils. This internal cycle helps in making phosphorus available for plants. 

Analytical method validation has developed within the pharmaceutical industry over the years in order to produce an assurance of the capabilities of an analytical method. A recent text on validation of analytical techniques has been published by the international Conference on Harmonisation (ICH) [19]. This discusses the four most common analytical procedures (1) identification test, (2) quantitative measurements for content of impurities, (3) limit test for the control of impurities and (4) quantitative measurement of the active moiety in samples of drug substance or drug product or other selected components of the drug product. As in any analytical method, the characteristics of the assay are determined and used to provide quantitative data which demonstrate the analytical validation. The reported validation data for CE are identical to those produced by an LC or GC method [11] and are derived from the same parameters, i.e. peak time and response. Those validation parameters featured by the ICH (Table 1) are derived from the peak data generated by the method. Table 1 also indicates those aspects of a CE method (instrumentation and chemistry), peculiar to the technique, which can affect the peak data and highlights factors which can assist the user in demonstrating the validation parameters. 

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