Probe electrospray ionization coupled to a quadrupole time-Of-flight: A feasibility study for the detection of cocaine and its derivatives in oral fluid

Probe Electrospray Ionization (PESI) is an atmospheric pressure ionization method that can be directly coupled with a mass spectrometer to allow ultrafast analyses without chromatographic separation and with minimal sample preparation. Using the particular case of cocaine and its metabolites in human oral fluid, the main objective of the present study was to test the feasibility of a new hybrid system combining a PESI source and a quadrupole time-of-flight (QTOF). The best results were obtained for a sample preparation with a simple dilution of 100 µL of oral fluids in an ethanol / 10 mM ammonium formate buffer (50/50) and 10 µL deposited on a dedicated sample plate and introduced into the PESI source. For HRMS acquisition, an approach consisting in a full-mass scan ("untargeted approach" from 100 to 500 m/z; MS1) followed by a targeted scheduled MSMS acquisition (precursor ions of the 3 molecules of interest and their 3 internal standards; MS2) gave the best signals. The total time of analysis was 0.45 min and the method was validated according to ISO15189 standard for a 5-100 ng/mL range, including accuracy and precision (inter-day and intra-day precision and bias values were lower than 15 %), matrix effect, carryover and specificity (no interference with a mixture of 119 psychotropic drugs spiked at 1 mg/L). The LLOD values were 1 ng/mL for the 3 cocaine derivatives and 83 Driving Under the Influence of Drug (DUID) cases sent to our Lab for the determination of illicit drugs in oral fluid were analyzed using the PESI-QTOF method and compared to a LC-MS/MS method. A perfect agreement was observed between the 2 methods, whether the cases were positive or negative. Cocaine was detected in 51 out of these 83 real cases (61.6 %). BZE and EME were also simultaneously detected in 50 of them (98.5 %). This feasibility study reports the first analytical method based on a coupling of a PESI source to a QTOF mass spectrometer. Adding the major advantage of high specificity through HRMS is a step forward for PESI technology.