Pharmaceutical assay characterization

It was apparent that the FDA recognized the ability of the pharmaceutical industry to develop chiral assays. With the advent of chiral stationary phases (CSPs) in the early 1980s [8, 9], the tools required to resolve enantiomers were entrenched, thus enabling the researcher the ability to quantify, characterize, and identify stereoisomers. Given these tools, the researcher can assess the pharmacology or toxicology and pharmacokinetic properties of enantiopure drugs for potential interconversion, absorption, distribution, and excretion of the individual enantiomers. 

The next section describes the utilization of //PLC for different applications of interest in the pharmaceutical industry. The part discusses the instrumentation employed for these applications, followed by the results of detailed characterization studies. The next part focuses on particular applications, highlighting results from the high-throughput characterization of ADMET and physicochemical properties (e.g., solubility, purity, log P, drug release, etc.), separation-based assays (assay development and optimization, real-time enzyme kinetics, evaluation of substrate specificity, etc.), and sample preparation (e.g., high-throughput clean-up of complex samples prior to MS (FIA) analysis). 

The overall workflow of ADME/Tox characterization of lead compounds is typically distributed across multiple departments or functional groups within pharmaceutical companies, often with specialized groups for different assays, analysis and interpretation. A representation of the overall workflow is provided in Figure 1.1. 

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). 

Bruno, J. Application of biosensor assays for the characterization of biopharmaceuticals. 4th Symposium on the Analysis of Well Characterized Biotechnology Pharmaceuticals. San Francisco, Jan. 9-12, 2000. 

The validity of any statement about the purity of a protein is directly linked to the quality of the analytical method used. The validation of immunoassay systems to detect protein impurities in rDNA pharmaceuticals must be achieved by careful production and characterization of the assay reagents. The studies presented here demonstrate that the blank run approach is reasonable for the isolation of reference materials and that high quality broad spectrum antisera can be produced to these mixtures. Significant improvements in assay sensitivity approaching the ppb level are attainable and should provide the methods to further improve product purity. 

Poor characterization of the physicochemical properties of liposomes Liposome behavior in vitro and in vivo is critically dependent on their physicochemical properties. Therefore a full physicochemical characterization of pharmaceutical liposomes is required in early stages of a development program (Table 5.6). In later development stages, these quality control assays can be used to obtain regulatory approval and to ensure batch-to-batch consistency. 

S. Gorog, The sacred cow The questionable role of assay methods in characterizing the quahty of bulk pharmaceuticals, J. Pharm. Biomed. Anal. 36 (2005), 931-937. 

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