Analysis of Psychotropic Drugs in Whole Blood Utilizing Simultaneous Scan/MRM Measurements (2)

Significance of the Topic

The accurate detection of psychotropic drugs in whole blood is essential for forensic investigations, clinical toxicology, and therapeutic monitoring. Combining broad-spectrum screening with targeted quantitation enhances both sensitivity and throughput, reducing the need for multiple analyses and accelerating result turnaround in demanding laboratory environments.

Objectives and Study Overview

This study presents a comprehensive workflow for simultaneous scan and multiple reaction monitoring (MRM) analysis of medicinal toxicants in whole blood using the Shimadzu GCMS-TQ8030. Key aims include:

• Implementing a dual-acquisition mode to capture both full-scan spectra and MRM transitions in a single injection.
• Leveraging a forensic toxicological database for rapid identification of approximately 500 psychotropic compounds.
• Demonstrating semi-quantitative capability for benzodiazepines and related drugs.

Methodology and Instrumentation

Pretreatment: Liquid-liquid extraction of whole blood was performed using EXtrelut® NT3 cartridges. An internal standard mixture of deuterated PAH isomers (1 µg/mL) was added for semi-quantitation.

Instrumentation Used:

• Gas Chromatograph–Mass Spectrometer: Shimadzu GCMS-TQ8030 triple quadrupole system.
• Column: Rxi®-5Sil MS, 30 m × 0.25 mm I.D., 0.25 µm film.
• Injection: Splitless mode with glass wool liner at 260 °C.
• Oven Program: 60 °C (2 min) ramped at 10 °C/min to 320 °C, held 10 min.
• Interface Temp.: 280 °C; Ion Source Temp.: 200 °C.
• Acquisition: Simultaneous scan (m/z 45–700 at 5,000 u/sec) and high-speed MRM (0.15 s event time) optimized for etizolam and triazolam transitions.

Main Results and Discussion

Simultaneous scan/MRM analysis of extracted whole blood allowed the detection and identification of triazolam and etizolam via their optimized transitions, while full-scan data enabled screening of non-targeted benzodiazepines such as diazepam and desmethyldiazepam. Use of the forensic toxicological database provided estimated retention indices, quantitative and reference ions, and library spectra matching, improving confidence in identification even at low concentrations. Comparison with conventional total ion chromatogram (TIC) library searches demonstrated faster screening and enhanced detection limits for co-eluting or low-abundance analytes.

Benefits and Practical Applications

• High throughput screening and targeted quantitation in a single run reduces analysis time and solvent consumption.
• Comprehensive coverage of over 500 psychotropic compounds supports forensic casework and clinical assays.
• Semi-quantitative reporting using internal standards enables rapid concentration estimation for abuse-related compounds.

Future Trends and Opportunities

Advances in high-speed data acquisition and expanded compound libraries will further enhance simultaneous scan/MRM workflows. Integration with automated sample preparation and data processing pipelines will enable fully automated screening platforms. Emerging technologies such as ion mobility spectrometry coupled with GC-MS/MS may provide additional separation dimensions for complex biological matrices.

Conclusion

The demonstrated workflow using Shimadzu’s GCMS-TQ8030 enables efficient, sensitive, and comprehensive screening of psychotropic drugs in whole blood. Simultaneous scan/MRM acquisition combined with a comprehensive forensic toxicological database accelerates identification, improves confidence for low-level analytes, and supports semi-quantitative assessments, offering significant advantages for forensic and clinical laboratories.

References

• Shimadzu Corporation. Application Data Sheet LAAN-J-MS-E075: Analysis of Psychotropic Drugs in Whole Blood Utilizing Simultaneous Scan/MRM Measurements. First Edition, January 2013.
• Shimadzu Corporation. Application Data Sheet No. 74: Mass Separation of Cholesterol from Triazolam and Etizolam in Whole Blood. January 2013.