The application of chemical derivatization to clinical drug analysis.
The sensitivity and selectivity achievable in the analysis of drug substances from biological matrices is often limited by the physical and chemical properties of the analyte. These limitations are further exacerbated by the inherent reactivity of most drugs in biological systems (i.e., their propensity for undergoing biotransformation). One very powerful approach that has been taken to improve the quality of the analytical methodology is to alter the physico-chemical properties of the drug through chemical modification (derivatization) during some stage of the analytical sequence. This approach has been successfully applied to situations and has resulted in improved chemical stability, analytical selectivity and sensitivity. In most cases, drug analysis from biological fluids involves a chromatographic step; the derivatization reaction can be carried out either prior or subsequent to chromatography. In this paper, examples of the advantages (and limitations) offered by the introduction of a chemical derivatization step in clinical drug analysis will be presented. Specifically, focus will be placed on analysis of chemically-reactive antineoplastic agents and peptides/proteins. The latter represent an emerging class of drugs which present significant analytical challenges. The use of o-phthalaldehyde analogues offering improved derivative stability and increased sensitivity will be described.
D001826:Body Fluids / Q000032:analysis; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D002945:Cisplatin / Q000032:analysis; D004640:Emetine / Q000032:analysis; D006801:Humans; D010455:Peptides / Q000032:analysis; D004364:Pharmaceutical Preparations / Q000032:analysis*; D013629:Tamoxifen / Q000032:analysis
D010455:Peptides; D004364:Pharmaceutical Preparations; D013629:Tamoxifen; D002945:Cisplatin; D004640:Emetine