Microsampling with a Solid-Phase Extraction Cartridge: Storage and Online Mass Spectrometry Analysis

This study aims to introduce the concept of utilizing a solid-phase extraction (SPE) cartridge for remote biofluid collection, followed by direct sample analysis at a later time. For this, a dried matrix spot was prepared in a syringe, in the form of SPE cartridge for the first time to enable small biofluid collection (microsampling), storage, shipment, and online electrospray ionization (ESI) mass spectrometry (MS) analysis of the stored dried samples. The SPE sorbents were packed into an ESI syringe and the resultant cartridge was used for sampling small volumes (<20 μL) of different complex biological fluids including blood, plasma, serum, and urine. The collected sample was stored in the dry state within the confinement of the SPE sorbent at room temperature, and analyte stability (e.g., diazepam) was maintained for more than a year. Direct coupling of the SPE cartridge to MS provides excellent accuracy, precision, and sensitivity for analyzing illicit drugs present in the biofluid. The corresponding mechanism of wrong-way positive ion generation from highly basic elution solvents was explored. Without chromatography, our direct SPE-ESI-MS analysis technique afforded detection limits as low as 26 and 140 pg/mL for raw urine and untreated plasma, respectively. These promising results proved that the new syringe-based SPE cartridge can serve as a good alternative to conventional microsampling techniques in terms of analyte stability, ease of operation and versatility, and analytical sensitivity and speed.