During the development of a broad screening method for the analysis of drugs in whole blood on a benchtop GC-MS, the acylation of drugs with pentafluoropropionic anhydride (PFPA) was examined.
Seventy-eight drugs with functional groups potentially suitable for acylation were reacted with PFPA and analysed by GC-MS. In some cases, the low resolution EI mass spectrum obtained from a GC peak was not sufficent to identify the derivatization product due to the absence of a molecular ion and/or the occurrence of significant mass spectral fragment ions which could not be readily related to the parent drug or its expected derivative. Consequently, additional data obtained from CI and high resolution EI mass spectrometry was required to identify some derivatization products.
Apart from some drugs which formed either no derivative or gave multiple GC peaks, 17 formed unusual derivatization products following reaction with PFPA. Generally, unusual products were not formed at a 1° or 2° amine group on a drug but at alcohol or 1° amide groups. Dehydrated parent drugs and dehydrated drug acylated at other sites were the most commonly occurring of these unusual derivatization products.
Examples of drugs and proposed reactions and products follow, with references to related previous reports.
| enol formation [1] | oxycodone | bis-PFP |
| dehydrogenation [2] | desipramine | bis-PFP |
| decarboxylation | captopril | bis-PFP |
| dehydration of 1°amide [1,3] | disopyramide | underivatized (nitrile formation) |
| dehydration of an alcohol | labetolol warfarin | bis-PFP (doubly dehydrated) underivatized |
| deamidation | carbamazepine tolbutamide | PFP and underivatized PFP and underivatized |
| unexplained rearrangements | cimetidine lorazepam | PFP-cimetidine product PFP-lorazepam product |
This investigation showed that the identity of a derivative produced following the reaction of a new drug with PFPA should not be assumed.