Analysis of Opioids Using Isotope Dilution with GCMS-TQ8030 GC/MS/MS

Development of methods for analysis of drugs of abuse has become a high priority for both forensic toxicology and law enforcement. The large numbers of individual drugs and new "designer drugs" has made method development for these compounds a significant undertaking.

Gas chromatography mass spectrometry (GCMS) has been used extensively for analysis of drug residues and trace-level drugs in biological fluids. The most significant challenges have been matrix interference and achievement of meaningful detection limits for the compounds of interest. Triple quadrupole GC/MS/MS has emerged as a powerful technique for trace-level analysis in these complex biological matrices. Operation of the triple quadrupole GC/MS/MS in the Multiple Reaction Monitoring (MRM) mode provides exceptional sensitivity, selectivity, and specificity for detection and quantitation of targeted drugs in the presence of background interferences.

The isotope dilution technique, using isotopically-labeled analogs of target compounds as internal standards, is a widely used analytical approach for precise quantitation in drug assays. However, in many cases, when using deuterium-labeled analogs the mass spectra differ only slightly from the corresponding unlabeled compounds. The challenge is complicated when the native and labeled compounds completely or partially co-elute, as they often do, and the spectra overlap. Combining the specificity of unique MRM transitions for close-eluting native and labeled analogues, with the sensitivity of triple quadrupole MRM transitions is a powerful technique for unambiguous, quantitative determination of this important compound class.

This application note presents instrument configuration, operating parameters, and analytical results for analysis of a common narcotic, hydrocodone, using the isotope dilution technique paired with the specificity of the MRM analysis mode of the Shimadzu GCMS-TQ8030 triple quadrupole GC/MS/MS. Internal standard calibration of codeine and oxycodone was also included in the study.