Improving gas chromatographic determination of residual solvents in pharmaceuticals by the combined use of headspace solid-phase microextraction and isotopic dilution

Cyclohexane and toluene were gas chromatographically determined via headspace solid-phase microextraction both in ketoprofen drug substance and ketoprofen capsules by a procedure relying on isotopic dilution (ID), an analytical tool derived from mass spectrometry (MS). This approach, using an internal standard method, gave mean precision and accuracy (RSD 2.56%, 2.97% and bias 0.21%, −0.99% for cyclohexane and toluene, respectively) not obtainable by the more commonly used external standard ones in the presence of real sample matrices. Optimisation of the operative conditions was also supported by experimental design. More generally, the proposed method, exploiting ID without resort to the costly MS instrumentation, could be recommended whenever opportune deuterated analogues of the target analytes and GC capillary columns able to separate all the peaks involved are ready available on the market.