A Novel Platform of On-line Sample Pre-treatment and LC/MS/MS Analysis for Screening and Quantitation of Illicit Drugs in Urine

In recent years, LC/MS/MS methods are adopted in analyses of illicit and prescription drugs in toxicological samples such as urine and serum. Sample pre-treatment is always a critical step in the whole analysis procedure and on-line sample pre-treatment is desired not only for improving analysis throughput, but also minimizing human errors. The CLAM-2000 module is designed for on-line sample pre-treatment in high throughput LC/MS/MS analysis of drugs and metabolites in biological samples such as plasma/serum and urine. Many sample preparation process can be performed automatically such as dispensing solvents, sample-reagent mixing by vortexing, sample filtering by vacuum filtration, and sample derivatisation with heating. Internal standard and reagent for derivatization or other purposes can be added to a sample before or after protein crash. We describe development of an automated sample pre-treatment using a Shimadzu CLAM-2000 module coupled with Shimadzu LCMS-8040 TQ system. It involves IS addition, protein precipitation, filtration and transferring the final solution to LC/MS/MS for analysis. This new platform was applied and evaluated for quantitation of 18 illicit drugs with 14 isotope-labelled internal standards (IS).