I am trying to determine the extraction efficiency of amphetamine, methamphetamine, MDA and MDMA with metycaine as the internal standard (alternative internal standard such as deuterated cannot be used) by GC-MS. To do so, I have processed two sets of sample. In the first set of sample, I spiked my matrix with the drugs, extract the sample and added the internal standard at the very last step of the extraction process. In the second set of sample, I add neat standard and internal standard. I dried down the mixture with air and no heat followed by reconstitution with the same volume of solvent as the first set.

For each set of data, I divide the target ion response by the internal standard ion response. The division of this ratio obtained from my extracted sample (i. e. the first set) by that obtained from my non-extracted sample (i. e. the second set) will give me the extraction efficiency.

Unfortunately, I always get an extraction efficiency >100%. So, I think I must have lost some of my drugs during the drying step for my non-extracted sample. I have tried adding 20 ul of hydrochloric acid/methanol to 100 ul of my non-extracted sample. But the GC-MS gives me smeared peaks. Anyone knows what's going on and how I can solve this problem? Many thanks.