Pharmaceutical Analytes

Capillary electrophoresis employing chiral selectors has been shown to be a useful analytical method to separate enantiomers. Conventionally, instrumental chiral separations have been achieved by gas chromatography and by high performance liquid chromatography.127 In recent years, there has been considerable activity in the separation and characterization of racemic pharmaceuticals by high performance capillary electrophoresis, with particular interest paid to using this technique in modem pharmaceutical analytical laboratories.128 130 The most frequently used chiral selectors in CE are cyclodextrins, crown ethers, chiral surfactants, bile acids, and protein-filled... 

A. Legin, A. Rudnitskaya, D. Clapham, B. Seleznev, K. Lord, and Y. Vlasov, Electronic tongue for pharmaceutical analytics quantification of tastes and masking effects. Anal. Bioanal. Chem. 380, 36-45 (2004). 

Part—IV has been entirely devoted to various Optical Methods that find their legitimate recognition in the arsenal of pharmaceutical analytical techniques and have been spread over nine chapters. Refractometry (Chapter 18) deals with refractive index, refractivity, critical micelle concentration (CMC) of various important substances. Polarimetry (Chapter 19) describes optical rotation and specific optical rotation of important pharmaceutical substances. Nephelometry and turbidimetry (Chapter 20) have been treated with sufficient detail with typical examples of chloroetracyclin, sulphate and phosphate ions. Ultraviolet and absorption spectrophotometry (Chapter 21) have been discussed with adequate depth and with regard to various vital theoretical considerations, single-beam and double-beam spectrophotometers besides typical examples amoxycillin trihydrate, folic acid, glyceryl trinitrate tablets and stilbosterol. Infrared spectrophotometry (IR) (Chapter 22) essentially deals with a brief introduction of group-frequency... 

Polar analytes in the m/z 100-1500 range are often involved in pharmaceutical analytics including metabolism studies. The types of ions formed are various and depend on the ion polarity, the pH of the solution, the presence of salts, and the concentration of the sprayed solution. Multiply charged ions are rarely observed. 

Ion chromatography has become an essential tool of the pharmaceutical analytical chemist. The high sensitivity of the technique, coupled with the wide dynamic operating range made possible with modern high-capacity stationary phases makes it ideal for the analysis of ions in pharmaceutical applications. The combination of gradients and suppressed conductivity detection provides a powerful screening... 

Abbott Laboratories, Pharmaceutical Analytical Research and Development, North Chicago, IL... 

Laboratory of Pharmaceutical Analytical Chemistry, School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Bd dYvoy 20, CH-1211 Geneva 4, Switzerland... 

Ensuring that the instrument to be used performs correctly is the first step in developing an instrumental methodology. The European Pharmacopoeia and the guidelines of the Pharmaceutical Analytical Sciences Group (PASG) recommend that NIR instruments be qualified as per the manufacturer s instructions, which should include at least the following ... 

The strict regulations of the pharmaceutical industry have a significant effect on the quality control of final products, demanding the use of reliable and fast analytical methods. The capacity that the technique has for the simultaneous determination of several APIs with no need of, or with minimum, sample preparation has considerably increased its application in pharmaceutical analytical control. The main limitation of NIR is the relatively low sensitivity that limits the determination of APIs in preparations when their concentration is less than 0.1%. Nevertheless, instrumental improvements allow the determination below this limit depending on the nature of the analyte and the matrix, with comparable errors to the ones obtained with other instrumental techniques. The reference list presents an ample variety of analytical methodologies, types of samples, nature of analyte and calibration models. A detailed treatment of each one is beyond the scope of... 

PASO Pharmaceutical Analytical Sciences RET resonance energy transfer... 

The development of a plethora of HPLC CSPs in the 1980s and 1990s has, to a large extent, made the use of chiral mobile-phase additives (CMPAs) redundant in most modem pharmaceutical analytical laboratories [23]. Before this period, chiral selectors were used routinely as additives in HPLC, but are now only used for a small number of specific applications [23]. CMPAs are used to form... 

Oxadiazoles and their benzo derivatives find use in applications as diverse as pharmaceuticals, analytical reagents, propellants and explosives, starting materials in organic synthesis, and for polymer preparation and modification. 

The ion formation may occur in the bulk solution before the electrospray process takes place or in the gas phase by protonation or salt adduct formation, or by an electrochemical redox reaction. Polar compounds already exist in solution as ions therefore, the task of the electrospray is to separate them from their counterions. This is the case of many inorganic and organic species and all those compounds that show acidic or basic properties. Proteins, peptides, nucleotides, and many other bio- and pharmaceutical analytes are typical examples of substances that can be detected as proto-nated or deprotonated species. 

Dissolution testing is one of the most common analytical techniques performed in a pharmaceutical analytical laboratory. It is performed primarily on oral dosage forms to determine the in vitro release of a drug from its finished dosage. Dissolution testing complements other analytical tests that are used to characterize the performance of the final dosage form (e.g., potency and related substances assay). 

M. Freeman, M. Leng, D. Morrison, and R. P. Munden from the UK Pharmaceutical Analytical Sciences Group (PASG), Position paper on the qualification of analytical equipment, Pharm. Technol. Eur., pp. 40-46, Nov. 1995. 

Renger, B., Jehle, H., Fischer, M., and Funk, W. Validation of analytical procedures in pharmaceutical analytical chemistry HPTLC assay of theophylline in an effervescent tablet. J Planar Chrom 8 269-278 (July/Aug. 1995). 

Pharmaceutical Analytical Development, AstraZeneca R D Molndal, Sweden... 

Pharmaceutical analytical chemists continue to seek more sensitive techniques for the determination of drug plasma concentrations and have looked beyond... 

There are many types of HPLC detectors available today with the most popular ones including UV and UV-photodiode array (PDA), fluorescence, refractive index, evaporative light scattering (ELSD), charged aerosol (CAD), and the mass spectrometer. Of these, the most commonly used detector for pharmaceutical analytical methods is the UV detector since a majority of pharmaceutical compounds have some type of chromophore. Multiple detectors in series can also be utilized in order to obtain more information per chromatographic run. For example, a PDA detector can... 

S. Ahuja, Chromatographic solution to pharmaceutical analytical problems, Chromatographia, 34 411 (1992). 

Two different types of internal standards are used. The first and usually ideal choice is a stable isotope of the analyte itself. In most cases, 13C or 2H isotopes are used for this purpose. It is important to note that the number of atoms replaced by the stable isotope should be large enough in order not to overlap with the natural isotope distribution of the analyte. The replacement of 6 12C or 6 1H atoms by 13C or 2H is usually a good choice for most pharmaceutical analytes (m/z < 500). Such isotopes are ideal as internal standards since they will have identical properties in terms of the ionization efficiency and sensitivity, but also in terms of the sample preparation procedure (solubility, extraction rate and so forth). They will have an identical retention time and will therefore correct any fluctuations on the chro-... 

In the example in Figure 4-47, the retention of pharmaceutical analyte X was first altered by decrease of mobile-phase pH (Figure 4-47A), and in the second case (Figure 4-47B) the pH was maintained constant and the concentration of counteranion was increased via addition of its sodium salt. The resulting effect on the retention of basic analyte is strikingly similar if both dependencies are plotted against the concentration of free counteranions of CIOt, as shown in Figure 4-48. 

Therefore, a system suitability test with a known set of probes such as MIX 1 could be used as an internal test to provide further conhdence in regard to the batch-to-batch reproducibility of the packing material and/or to observe if the bonded phase has been compromised. This could also be used to probe the lot-to-lot reproducibility of new types of stationary phases that are available on the market. Once this simple and fast system suitability test is performed with MIX 1 and acceptable results are obtained using a set of defined acceptance criteria, the analysts may commence with his/her analytical method and run the specihc system suitability test stated in the method for their particular target pharmaceutical analyte. 

R. LoBrutto, A. Jerkovich, A. Jones, T. Prowse, and R. Vivilecchia, UPLC —A critical look at system/column performance and method transfer considerations for pharmaceutical analytes, HPLC 2005 Conference, Stockholm, Sweden, 2005. 

Method validation is a process by which documented evidence is prepared and provided to show that the method meets the intended need. Highly regulated pharmaceutical analytical laboratories perform method validation and generate data on the following parameters, to comply with the compliance requirements of government agencies such FDA, EPA and/or to provide data for compendial agencies like USP, BP, etc. 

Karnes, H.T. Shiu, G. Shah, V.P. Validation of hioana-lytical methods. Pharm. Res. 1991, 8 (4), 421-426. Renger, B. Jehle, H. Fischer, M. Funk, W. Validation of analytical procedure in pharmaceutical analytical chem-... 

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