The development of analytical methods for the detection and quantitation of drugs and metabolites in a range of biological matrices is a challenging process. Forensic toxicology labs need a reproducible and reliable methodology to ensure the robustness of the data and the quality of the results. They also need robust and sensitive instrumentation that can detect drugs at trace levels with high specificity, especially when it comes to novel psychoactive substances (NPS), which can be difficult to monitor and control.

This blog discusses the use of nominal mass spectrometry for the targeted analysis of NPS. Triple quadrupole and QTRAP mass spectrometers, which can be used for both screening and confirmation workflows, are considered the gold standard for routine, high-sensitivity detection and quantitation of NPS due to their ability to measure the concentration of these substances at low levels with accuracy and good reproducibility. From detecting to identifying and quantifying NPS, nominal mass spectrometers can do it all.

Triple quadrupole and QTRAP mass spectrometers provide scanning functions to address the various testing needs of targeted quantitative workflows. Let’s take a closer look at how these functions can be used for NPS testing.

The power of the triple quadrupole system: sensitivity and selectivity

Triple quadrupoles consist of three quadrupole mass analyzers in a sequence. The first quadrupole isolates a selected precursor ion, the second serves as a collision cell for fragmentation and the third detects specific product ions. When performing quantitative analysis,  multiple reaction monitoring (MRM) is the most commonly used operation mode on a triple quadrupole.  MRM mode works like a double mass filter which drastically increases sensitivity and specificity. As a result, this scan mode enables precise quantitation and identification of specific ions in various matrices, which is greatly beneficial when detecting challenging NPS in complex biological fluids.

Multiple reaction monitoring (MRM) scans can be used with triple quadrupole systems and with QTRAP systems operating in triple quadrupole mode. MRM is the most popular scanning function used on nominal mass instruments to detect and quantify NPS. MRM provides a highly specific and sensitive detection method that enables quantitation of analytes with the lowest limits of detection, excellent reproducibility and a wide linear range. MRM ratios (the ratio of quantifier and qualifier of the analyte MRM transitions) can also be used for an added level of specificity to qualitatively confirm the presence of a drug or metabolite in a forensic case sample, which in some cases can prevent forensic toxicologists from reporting a false positive confirmation result if the ion ratio criteria fails for that specific analyte.

Check out this technical note to see how the Scheduled MRM algorithm can be used on the QTRAP 4500 system in triple quadrupole mode to analyze the main psychoactive components of kratom, a scheduled NPS that has risen in popularity on the recreational drug market.

The QTRAP system advantage: simultaneous quantitation and confirmation

QTRAP systems are hybrid triple quadrupole linear ion trap (LIT) mass spectrometers. They are based on triple quadrupole mass spectrometers and, as mentioned earlier, can be operated as triple quadrupole mass analyzers. However, QTRAP systems provide additional qualitative scan functions that can be used to improve selectivity beyond the capabilities of triple quadrupole systems. These unique LIT scanning functions enable high-quality MRM quantitation with simultaneous identification and confirmation capabilities.

Enhanced product ion (EPI) scans (full MS/MS scans) can be triggered when the signal is detected for each specific MRM transition. This results in the generation of a full-scan MS/MS spectrum that can be used to significantly improve confidence in compound identification through spectral library matching for both analyte confirmation and identification. This technical note demonstrates how an EPI scan was used to acquire a full-scan MS/MS spectrum of an NPS through spectral library matching.

MRM³ scans enables robust quantitation from second-generation fragment ions, which significantly improves selectivity and reduces—and in most instances, eliminates—the matrix background signal. The result is lower limit of quantitation (LOQ) concentrations, due to improved signal to noise, and improved quantitation. Read this technical note to learn how the MRM³ workflow was used to increase selectivity and provide a 5-fold improvement in sensitivity over MRM for the analysis of 11-nor-9-carboxy-THC (THC-COOH), a marker of cannabis consumption, in oral fluid.

Fit for purpose solution tailored to your NPS analysis needs

In summary, triple quadrupole and QTRAP mass spectrometers are workhorses for targeted NPS analysis. Triple quadrupole scans provide the highest performance levels for quantitative workflows due to their sensitivity and selectivity. The MRM workflow enables accurate and sensitive detection of the most challenging NPS and their metabolites while maintaining reliable quantitation over a wide range of concentrations. QTRAP systems offer unique scanning functions that provide added specificity and increased confidence in NPS identification.

Together, these nominal mass platforms provide the required levels of selectivity and sensitivity to meet your specific lab requirements and budget while providing the highest performance levels for quantitative and qualitative workflows.

NOMINAL MASS SOLUTIONS FROM SCIEX

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Powerful scan modes of QTRAP system technology
Learn how the combination of triple quadrupole and linear ion trap analyzers enables quantitative and qualitative experiments on the same platform with no compromise.
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