Qualitative Screening of Drugs in Whole Blood by DPiMS QT installed LCMS-9030

Significance of the Topic

The rapid and reliable identification of drugs in biological matrices is critical in forensic investigations, clinical toxicology and quality control laboratories. Traditional LC–MS/MS protocols often require laborious sample preparation and chromatographic separation, extending analysis time. The combination of direct probe ionization with high–resolution quadrupole time–of–flight analysis offers an opportunity to accelerate workflow and maintain confidence in compound identification.

Objectives and Study Overview

This study demonstrates a qualitative screening approach for 17 common drug compounds spiked into human whole blood using the DPiMS™ QT electrospray ionization probe integrated with a Shimadzu LCMS™-9030 Q-TOF mass spectrometer. Key aims include minimizing sample preparation, eliminating liquid chromatography, reducing analysis time to three minutes, and obtaining comprehensive MS/MS data via the newly developed iDIA acquisition method.

Methodology and Instrumentation

Whole blood samples were spiked at 500 ng/mL with 17 target drugs. Ten microliters of this spiked blood were diluted with water and ethanol, centrifuged, and the supernatant directly applied onto a sample plate. The DPiMS QT probe repeatedly sampled and electrosprayed the analyte. The iDIA method employed narrow 1 Da precursor isolation windows to acquire MS/MS spectra for all ionized compounds in rapid succession.

Instrumentation

• DPiMS™ QT probe kit for electrospray sampling
• Shimadzu LCMS™-9030 quadrupole time-of-flight mass spectrometer
• Operating conditions: positive ion mode, DL temperature 250 °C, heat block 50 °C, interface voltage 3.5 kV
• Acquisition ranges: TOF-MS m/z 120–770; MS/MS m/z 20–780 with collision energy ramp 10–50 V

Main Results and Discussion

All 17 spiked drugs were successfully identified within a total measurement time of three minutes. Library matching scores ranged from 84 to 100, demonstrating robust spectral fidelity. Narrow precursor windows effectively reduced interferences from co-eluting matrix components and isotopic overlaps. Representative MS/MS spectra matched closely to high-resolution library standards, confirming reliable compound identification even without chromatographic separation.

Benefits and Practical Applications

• Minimal sample preparation: simple dilution and centrifugation
• Rapid analysis: full qualitative screen in 3 minutes per sample
• Elimination of LC separation reduces solvent use and maintenance
• Comprehensive MS/MS data supports confident identification in complex matrices

Future Trends and Applications

Further developments may include automation of sample spotting for high-throughput screening in clinical and forensic laboratories. Integration with quantitative workflows and expansion of spectral libraries will broaden target panels. Advances in data processing and AI-driven spectral matching could enhance speed and accuracy. The platform may also be adapted for environmental, food safety or doping control applications where rapid screening is vital.

Conclusion

The coupling of DPiMS QT direct electrospray ionization with LCMS-9030 Q-TOF and the iDIA acquisition strategy enables ultrafast, reliable qualitative screening of drugs in whole blood. This workflow dramatically streamlines analysis by removing chromatographic steps, achieving high identification confidence with minimal sample preprocessing and a 3-minute run time.

References

• E. Imoto, T. Murata. Qualitative Screening of Drugs in Whole Blood by DPiMS QT-Installed LCMS-9030. Shimadzu Application News, First Edition: Sep. 2021.