Challenges in GC-MS analysis: Case studies on phenibut and ethylphenidate

•Challenges on GC-MS analyses of thermal labile compounds was addressed.•Thermal labile phenibut was identified by GC-MS through derivatisation.•Degradation of methyl/ethylphenidate was reduced by modifying GC-MS parameters.

The challenges associated with drug analysis using GC-MS such as thermal degradation, cyclisation or unwanted side reactions causing potential erroneous identification have become evident in view of the high surge in new drugs available in the market. Two case studies illustrated how alternative methods or modifications to existing techniques can help to circumvent the limitations. In the first case study, phenibut which is a GABA analogue, cyclises to 4-phenyl-2-pyrrolidinone under thermal conditions. The identification of phenibut was achieved through derivatisation and identification of its TMS derivative. The second case study, thermal degradation was minimised on drugs of interest methylphenidate and ethylphenidate by reducing the injector port temperature to 200 °C and maintaining the GC oven temperature at below 190 °C in order to prevent thermal degradation of the drugs of interest.