Drug development matrix problems

In the last case, this may be a physical problem resulting from incomplete penetration by the extraction solvent into the matrix. Alternatively, incomplete recovery of the analyte may result from chemical binding between the analyte and a constituent of the matrix. This is particularly important in the determination of drugs in body tissues where binding to proteins is known to occur. Problems of this kind are documented in the literature. If a new procedure is being developed, it is necessary to investigate the extraction step, e.g. by using radioactive tracers. 

The solution to this problem has been the development of oral slow-release preparations - formulations of the drug in a matrix from which it slowly leaches out allowing for intestinal absorption over a period of many hours. Tmax for these preparations may be as high as 10-12 hours after ingestion. 

In general, it is easier (and faster) to develop an HPLC-ESI-MS/MS method for multiple analytes with the matrix effects identified and under control as compared to IA (see below). Furthermore, selectivity and interference from matrix components and/or metabolites is less of a problem with an LC-MS/MS method compared to IA. With an appropriate internal standard (IS), LC-MS/MS methods are more precise than IA. Moreover, the LC-MS/MS calibration range is broader and can accommodate disproportionate concentration ranges of the drug compound and its metabolites. In contrast, most IA are geared to quantify only one analyte at a time because the method development of multiplex IA is complicated and often cannot be optimized for all analytes of interest. 

Numerous detection systems based on almost all kinds of known analytical techniques have been developed for screening, identifying, and quantifying drug residues in food. Each detection system has its own advantages and drawbacks which must be carefully considered in the selection of the most convenient system for a particular analyte in a particular matrix. The problem of analyzing for drug residues in food is complicated by the fact that it is not known whether residues exist and, if they exist, the type and quantity are not known. 

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