Mechanism of interferences for gas chromatography/mass spectrometry analysis of urine for drugs of abuse

Abstract

Although gas chromatography/mass spectrometry (GS/MS) is recognized as the definitive procedure for confirming positive immunoassay screening results of urine for drugs of abuse, targeted GC/MS analysis does have limitations. False negative results can occur when interfering drugs are present at high relative concentrations. If an interfering drug competes with the targeted drug for the derivatization reagent, low results are produced. If the interfering drug chromatographically co-elutes with the target drug, the ionization efficiency of the target compound by electron impact (EI) ionization may be affected. False positive results can also occur through a number of mechanisms. Two substances with the same mass spectrum require gas chromatographic conditions that enable adequate separation of the compounds prior to MS analysis. In the case of optical isomers, special columns or derivatives must be used for identification and quantification. The widespread use of selected ion monitoring may further limit GC/MS assays. Drugs that produce similar high molecular-weight mass fragment ions could potentially interfere if they have similar GC retention times and if inappropriate ions are selected for monitoring. The conversion of one drug to another by the GC/MS instrument itself is a particularly insidious problem. False positive and negative results have serious forensic consequences and must be recognized and avoided. In contrast, the consumption of poppy seeds or meats from livestock given drugs such as methenolone can produce unexpected true positive results for opiates and anabolic steroids, respectively.