Pharmaceutical quality control

In the case of pharmaceutical quality control, and in many other spheres, methods which give an answer in a shorter hme are being investigated, evaluated and in some cases used. Some of these quicker or rapid methods will be referred to in this sechon. 

In HPLC, a sample is separated into its components based on the interaction and partitioning of the different components of the sample between the liquid mobile phase and the stationary phase. In reversed phase HPLC, water is the primary solvent and a variety of organic solvents and modifiers are employed to change the selectivity of the separation. For ionizable components pH can play an important role in the separation. In addition, column temperature can effect the separation of some compounds. Quantitation of the interested components is achieved via comparison with an internal or external reference standard. Other standardization methods (normalization or 100% standardization) are of less importance in pharmaceutical quality control. External standards are analyzed on separate chromatograms from that of the sample while internal standards are added to the sample and thus appear on the same chromatogram. 

Capillary electrophoresis (CE) methods for pharmaceutical quality control (QC) analysis are developed and applied in early to late phase of development. Although there are many application areas in early development as will be covered in other chapters of this book, this chapter will emphasize the late phase development of low-molecular-weight compounds. Nevertheless, the approaches that are discussed for late phase development may also be applied for early methods and to high-molecular-weight compounds. 

Wynia, G. S., Windhorst, G., Post, P. C., and Maris, F. A. (1997). Development and validation of a capillary electrophoresis method within a pharmaceutical quality control environment and comparison with high-performance liquid chromatography. /. Chromatogr. A 773(1—2), 339—350. 

Baseline separation of the cephalosporin antibiotic cephradine, its main impurity cephalexin, and other related impurities was achieved by MEKC. The method was validated in compliance with the USP XXII analytical performance parameters and the results were comparable with a validated LC method, depicting CE to be a valuable alternative technique to LC in pharmaceutical quality control. In most cases, the amount of impurities relative to the main compound measured by MEKC is similar to that obtained by LC. However, some reports reveal that there are differences in number and amount of impurities between MEKC and LC analysis. MEKC permitted the determination of seven known and three unknown impurities in cefotaxime and the results were in good agreement with those of LC. ° MEKC yielded a higher amount of the cefotaxime dimer but a lower amount of an unidentified impurity with respect to LC. The differences may be due to the easier formation of the dimer in the aqueous sample solvent used in MEKC compared to the hydroorganic... 

Pluym, A., Van Ael, W., and De Smet, M. (1992). Capillary electrophoresis in chemical pharmaceutical quality-control. TrAC, Trends Anal. Chem. 11, 27—32. 

Thomas, B. R., and Ghodbane, S. (1993). Evaluation of a mixed micellar electrokinetic capillary electrophoresis method for validated pharmaceutical quality-control. /. Liq. Chromatogr. 16, 1983-2006. 

Pluym et al. compared the use of CE to that of HPLC in chemical and pharmaceutical quality control. They stated that CE could be considered as a complementary technique to HPLC because of its large separation capacity, its simplicity, and its economical benefits. Jimidar et al. decided that CE offers high separation efficiency and can be applied as an adjunct in HPLC method validation. Mol et al. evaluated the use of micellar electrokinetic chromatography (MEKC) coupled with electrospray ionization mass spectrometry (ESI—MS) in impurity profiling of drugs, which resulted in efficient separations. 

P. Corti, E. Dreassi, G. Ceramelli, S. Lonardi, R. Viviani and S. Gravina, Near Infrared Reflectance Spectroscopy applied to pharmaceutical quality control. Identification and assay of cephalosporins, Analusis 19, 198-204 (1991). J.K. Drennen and R.A. Lodder, Pharmaceutical applications of near-infrared spectrometry, in Advances in Near Infrared Measurements, vol. 1, G. Patonay (ed.), JAI Press, Greenwich, CT, pp. 93-112, 1993. 

Guide to Inspection of Microbiological Pharmaceutical Quality Control laboratories, Interpharm Press, Buffalo Grove, IL, 1993. 

Sukowski, L., and Ulmschneider, M. (2005), In-line process analytical technology on qualitative NIR modelhng An innovative approach for the pharmaceutical quality control, Pharmlnd, 67(7), 830-835. 

U.S. Food and Drug Administration (FDA) (1993), Guide to inspections of microbiological pharmaceutical quality control laboratories, FDA, Rockville, MD. 

Laboratory equipment and procedures must be qualified and validated. Every NDA/ANDA inspection will include both an evaluation of laboratory controls and procedures and an audit of some of the raw data used to generate results. These data may be located in research and development test logs. The authenticity and accuracy of data used in the development of a test method should be established. (See the Guide to Inspection of Pharmaceutical Quality Control Laboratories, July 1993.)... 

Acceptance criteria for precision depend very much on the type of analysis. For pharmaceutical quality control, precision of better than 1 % RSD is easily attained, while for biological samples the precision is more like 16% at the detection limit and 10% at higher concentration levels. For environmental and food samples, the precision is very much dependent on the sample matrix, the level of the analyte, and on the analytical method, being in the range of 2% to more than 20% RSD. Acceptable precision values as a function of the analyte concentration have been suggested (11) by the Association of Official Analytical Chemists (AOAC) peer-verified methods program (Table 25.1). 

Office of Regulatory Affairs, Food and Drug Administration Guide to Inspection of Pharmaceutical Quality Control Laboratories, July 1993 Website http //www.fda.gov/ora/inspect ref/igs/pharm.html. 

Guia para Inspecciones de Laboratorios de Control de Calidad Farmaceu-tica. English version Pharmaceutical Quality Control Labs. (Issued July 1993)... 

Guide to Inspection of Pharmaceutical Quality Control Laboratories, FDA, Washington, DC, July 1993. 

R Davis. A guide to inspection of pharmaceutical quality control laboratories. Pharmaceutical Engineering Sept./Oct. 1992. 

Applications of HPLC Of the bioanalytical separation technologies described in this book, arguably HPLC has the widest range of applications, being adopted for the purpose of clinical, environmental, forensic, industrial, pharmaceutical and research analyses. While there are literally thousands of different applications, a few indicators of how HPLC has been used are as follows (i) Clinical quantification of drugs in body fluids (ii) Environmental identification of chemicals in drinking water (iii) Forensic analysis of textile dyes (iv) Industrial stability of compounds in food products (v) Pharmaceutical quality control and shelf-life of a synthetic drug product (vi) Research separation and isolation of components from natural samples from animals and plants. 

Bouma, M., Nuijen, B., Jansen, M.T., Sava, G., Picotti, E., Elaibani, A., Bull, A., Beijnen, J. H. Development of a LC method for pharmaceutical quality control of the antimetastatic ruthenium complex NAMI-A. J. Pharm. Biomed. Anal. 31, 215-228 (2003)... 

To illustrate this principle, the interim results from a laboratory where electronic signatures have been designed into the process will be presented and discussed. The CDS is installed in a pharmaceutical quality control laboratory where the system is used for both raw material and finished product analysis there are approximately 50 part-time users of the system. The current CDS version was not fully comphant with the technical requirements of 21 CFR Part 11 and was to be upgraded to a new compliant version of the software from the same vendor. Before the implementation of the new version, the current process was mapped and analyzed to see if there were any opportunities for improvement and to make effective use of electronic signatures. 

R. Bryant, The Pharmaceutical Quality Control Handbook, Aster, Eugene, OR, 1989... 

The Division of Drug Analysis was established in 1952 and is responsible for pharmaceutical quality control and analysis in the Department of Medical Sciences within the Ministry of Public Health. It is separate and independent from the FDA but collaborates closely with the FDA in approving and monitoring the qualities and standards of the pharmaceutical products. 

Renger, B. Contemporary thin-layer chromatography in pharmaceutical quality control. /. AO AC Int., 81(2) 333-339, 1998. 

Klapper discusses NIR as a validatable tool in pharmaceutical quality control [30], while Moffat et al. [31] presented an excellent paper on how best to meet the ICH guidelines on validation. They used a quantitative method for paracetamol in tablets as an example for each guideline. 

A. Klapper, Use of NIR-Spectroscopy in Pharmaceutical Quality Control in Harmony with Official Specifications, Pharma Technol. J., 19(1), 81-85 (1998). 

Repeatability is obtained when the analysis is performed in one laboratory by one analyst using the same equipment at the same day. Repeatability should be tested by the analysis of a minimum of five determinations at three different concentrations (low, medium and high) in the range of expected concentrations, according to FDA [16], However according to the ICH [79] repeatability could be measured by the analysis of three determinations at three different concentrations or through six determinations at 100 % of the test concentration. The latter one is for analysis when the concentration is supposed to be constant for all samples, e.g., pharmaceutical products. The acceptance criteria for precision depends much on the type of analysis. For compound analysis in pharmaceutical quality control, precision should be better than 2 % [82], For bioanalytical applications the precision values at each concentration level should be better than 15 % except for the lower limit of quantification (LLOQ) where is should not exceed 20 % [16], The intermediate precision shows the variations affected in day-to-day analysis, by different analysts, different instruments etc. Reproducibility, as above, represents the precision obtained between different laboratories. 

The condensation of 1,2-naphthoquinone-4-sodiurn sulfonate with arterenol generates a-purple color which can be quantitated at 540 my. This procedure is selective for the primary amine in the presence of epinephrine and can be applied to pharmaceutical quality control.31 35 The sensitivity is lim-ited to 50 yg. 

In the pharmaceutical industry, preformulation is not generally carried out by one department alone. This activity integrates efforts of well-coordinated tasks among many research teams analytical research, basic pharmaceutics, quality control, dosage forms development, and others throughout the... 

Olson, B. A. and Tsang, P. K. S. Considerations for the development of separation methods for pharmaceutical quality control. Process Control Quality 10 25—39,1997. 

Practical Tip The risk of substance carryover in pharmaceutical quality control should be completely excluded by using microcaps once only. 

In the foregoing Sections on sample application, no recommendations were made regarding the arrangement of the samples on the plate. There are no hard and fast rules for using any particular sequence in either qualitative or semiquantitative analysis, and the user s final assessment of the appearance of the plate as a whole is at best based on experience. However, if a certain sequence for applying samples is adhered to, this considerably facilitates the assessment of thin-layer chromatograms for pharmaceutical quality control. 

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