Process-related impurities and

For many years, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) methods have been used as an essential tool to determine the hydrodynamic size, monitor product purity, detect minor product or process-related impurities, and confirm batch-to-batch consistency of protein and antibody products. ITowever, gel-based techniques have several limitations, such as lack of automation, varying reproducibility, and a limited linear range. SDS-PAGE is also labor-intensive and generates large volume of toxic waste. Most importantly, the technique does not provide quantitative results for purity and impurity determination of proteins and antibodies. 

Lorenz LJ, Bashore FN, Olsen BA. Determination of process-related impurities and degradation products in cefaclor by high-performance liquid chromatography. J Chrom Sci 1992 30 211-216. 

Is it a process-related impurity and, if so, at what step of the process is it formed ... 

Alsante, K.M. Hatajik, T.D. Lohr, L.L. Sharp, T.R. Isolation and identification of process related impurities and degradation products from pharmaceutical drug candidates, part I. Am. Pharm. Rev. 2001, 4 (1), 70-78. 

Isolation and identification of process related impurities and degradation products from pharmaceutical drug... 

Experimental campaign bulk or in-process control samples (e.g., prior to recrystallization) are excellent sources of process-related impurities and are a vital component of the KPSS. Isolated fractions collected from a preparative or semi-preparative liquid chromatography (LC) system are also excellent KPSS samples. Sometimes small-scale synthesis of the impurity or degradant is possible and less time-consuming than the isolation techniques. 

Chapter 14 provides practical guidance with case studies on isolating and characterizing process-related impurities and degradation products for pharmaceutical drug candidates. The case studies utilize isolation or synthesis in conjunction with mass spectral and NMR characterizations. A collaborative multiple disciplinary strategy has been found to be the most efficient way to solve impurity/degradation product problems. 

Lorenz, LJ. Bashore, F.N. Olsen, B.A. Determination of process-related impurities and d adation products in cefaclor by hi -performance liquid chromatography. J.Chromatogr.ScL, 1992,30,211— 216 determination, [simultaneous impurities, degradation products bulk gradient coliunn temp 25] Nahata, M.C. Jackson, D.S. Liquid chromatographic method for the determination of cefadroxil in its suspension and in serum. J.Liq.Chromatogr., 1990,13,1651-1656 [simultaneous cefadroxil sui n-sions cefaclor is IS]... 

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