High-sensitivity detection of therapeutic drugs in complex biofluids using a packed ballpoint-electrospray ionization technique.

A simple and sensitive C ₁₈ packed ballpoint-electrospray ionization (PBP-ESI) technique was developed for biofluid analysis. In this technique, the configuration of a commercial ballpoint consisting of a hollow chamber, an intermediate socket, and a metal ball was fully exploited. The rear-end hollow chamber was used for loading C ₁₈ adsorbent and sample, and the front metal ball served as a spray emitter for online ionization. The good electrical conductivity of the metal body allowed high voltage to be conveniently applied to the ballpoint without inserting the electrode into the solution for electrical connection. Urine sample was directly analyzed with the C ₁₈ packed ballpoint; plasma and whole blood samples were premixed with C ₁₈ adsorbent before being packed into the ballpoint for detection. As a result of the sample cleanup by C ₁₈ adsorbent, the salt matrix in the urine sample as well as the phospholipid and protein matrices in plasma and whole blood samples was significantly reduced. The lower limits of quantitation (LLOQs) for urine, plasma, and whole blood samples reached the subnanogram-per-milliliter level. Graphical abstract.