The SPME procedure developed in this paper allows an important reduction in sample treatment compared with other conventional techniques such as liquid–liquid and solid-phase extraction. Although SPME is usually applied in the headspace mode, we carried out extraction in the HS mode due to the complexity of plasma sample matrix. Thus, the use of calibration curves prepared with spiked blank blood provides accurate results for quantitation, isotopically labelled surrogate / internal standards also being required to correct the matrix effect. Moreover, the application of GC–MS provides a satisfactory sensitivity and selectivity avoiding most of the interferences from this type of complex biological matrix.