Laser Secondary Neutral Mass Spectrometry of Bi₃⁺ Sputtered Pharmaceuticals

High spatial imaging of pharmaceutical compounds in cells and tissues provides valuable insights into their effects and side effects in organic tissue. Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) is one of the few methods capable of providing label-free 2D and 3D subcellular imaging. However, many pharmaceutical molecules exhibit low ionization efficiency during the ion sputtering process. To address this limitation, a ToF-SIMS sister technique, Laser Secondary Neutral Mass Spectrometry (Laser-SNMS) can be used to postionize sputtered neutral species. In this work, Laser-SNMS has been studied for six pharmaceuticals, including carbamazepine, verapamil, imipramine, ciprofloxacin, tetracycline and rifampicin. The pharmaceuticals were desorbed using Bi₃⁺ primary ions and photoionization was performed with a 157 nm (7.9 eV) excimer laser. Intact molecular ions were detected for 5 of the 6 compounds, with the exception being rifampicin. For all of the pharmaceuticals, characteristic photoionized fragments over m/z 200 were detected. By varying the laser power density and the delay between the primary ion impact and the laser pulse, photofragmentation patterns that could be used for unambiguous compound identification were discovered. The ion yield was notably enhanced over ToF-SIMS for the molecular ion or large fragment ions for all of the compounds investigated.