Chemical derivatization for forensic drug analysis by GC- and LC-MS

Utilizing chemical derivatization (CD) to improve gas chromatographic (GC) and GC-mass spectrometric (MS) analysis of drugs has been abundantly studied and widely practiced, while in liquid chromatography (LC) and LC-MS, application of CD approaches is still at an early stage. Silylation, acylation, and alkylation are common CD reactions, long adopted by GC and GC-MS (including GC-MS/MS) methodologies, to improve analytes' stability and/or to optimize their extraction/separation and detection efficiencies. Highly polar and nonvolatile analytes are not amenable to GC-MS analysis without the CD step; however, CD can improve LC-MS analysis of highly polar analytes, especially those with low molecular weights. Many CD reagents developed for GC and GC-MS applications are also effective in LC-MS. Other CD reagents are developed for LC-MS to enhance analytes' performance under electrospray and atmospheric pressure ionization sources. Certain CD reagents are designed to facilitate analytes' fragmentation (upon collision-induced dissociation) in generating intense product ions for sensitive MS/MS detection. In this review, various CD reagents, reaction types, and application examples are presented and discussed, with emphases on GC-MS and LC-MS analysis of drugs of abuse.