An Experimental and Theoretical Study of Laser Postionization of Femtosecond Laser Desorbed Drug Molecules.

Femtosecond laser desorption postionization mass spectrometry using 7.9 eV single photon ionization (7.9 eV fs-LDPI-MS) detected three of four drug compounds previously found to have very low ionization efficiencies by secondary ion mass spectrometry (SIMS). Electronic structure calculations of the ionization energies and other properties of these four drug compounds predicted that all display ionization energies below the 7.9 eV photon energy, as required for single photon ionization. The 7.9 eV fs-LDPI-MS of carbamazepine, imipramine, and verapamil all showed significant precursor (M+) ion signal, but no representative signal was observed for ciprofloxacin. Furthermore, 7.9 eV fs-LDPI-MS displayed higher M+ signal and mostly similar fragment ions compared to standard 70 eV electron impact mass spectrometry. Ionization and fragmentation patterns are discussed in terms of calculated wavefunctions for the highest occupied molecular orbitals. The implications for improving lateral resolution and sensitivity of MS imaging of drug compounds are also considered.