GEN-MKT-18-7897-A
Mar 11, 2024 | Blogs, Forensic, SCIEX OS software, Toxicology, ZenoTOF 7600 system | 0 comments
Read time: 4 minutes
LC-MS/MS is a powerful analytical tool in forensic toxicology testing that can support a variety of testing regimes such as screening, confirmation and quantitative workflows. More specifically, analysis of NPS using LC-MS/MS provides many advantages, including the ability to reliably detect new drugs and their metabolites from a variety of biological matrices.
In this blog, we are going to discuss the benefits of accurate mass spectrometry for non-targeted NPS analysis and how those benefits can provide additional levels of confirmation. Forensic toxicologists are often concerned about screening for and identifying unknown substances that have recently surfaced on the recreational drug market. The speed and sensitivity of accurate mass spectrometers can be leveraged to perform MS scanning experiments to search for unknown molecular ions while also performing selective MS/MS scanning functions. This provides comprehensive compound fragmentation on all the analytes present in the sample. Because these fragments are acquired in high resolution, the detected NPS can be accurately identified through spectra library database searching.
Accurate mass spectrometers, such as quadrupole time-of-flight (QTOF) systems, are flexible platforms that can support both quantitative and qualitative analysis. Below are some of the most common acquisition methods that can be leveraged for both targeted and non-targeted workflows.
Targeted workflows:
Check out this tech note to learn how the MRMHR on the SCIEX X500R QTOF system was used for the quantitation and identification of low levels of NPS in human urine samples: Read now
Non-targeted workflows:
Acquisition methods such as data-dependent acquisition (DDA) and SWATH data-independent acquisition (DIA) can be leveraged to acquire high-resolution spectra from single sample sets in a routine testing laboratory environment.
Learn more about the benefits of DDA and SWATH DIA for non-targeted workflows.
And check out these technical notes that compare the two workflows for the screening and quantitation of NPS in biological matrices:
Fast Forensic Toxicological Screening and Quantitation in Under 3 Minutes
Expanding NPS screening capabilities in the forensic toxicology laboratory
In summary, QTOF systems are the mass spectrometers of choice for NPS screening because of their ability to acquire high-resolution accurate mass precursor and fragment data to improve confidence in NPS detection, providing added flexibility for non-targeted workflows. The use of accurate mass spectrometry for NPS analysis reduces the effects of complex matrices and background interferences, which results in higher data quality, lower LOQs and fewer false positives. Overall, the ability to acquire full MS/MS fragmentation spectra of all the analytes present in the samples enhances compound identification through spectral library matching. In addition, previously acquired data sets can be retrospectively analyzed to look for the presence of newly identified NPS should new questions about a sample arise.
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As an analytical strategy, middle-down mass spectrometry (MS) workflows characterize biotherapeutic proteins by analyzing large, digested protein fragments or defined subunits, rather than fully intact proteins (top-down) or digested peptides (bottom-up). A middle-down strategy combines the strengths of top-down and bottom-up approaches by delivering high sequence coverage and structural specificity while maintaining relatively simple sample preparation. In practice, middle-down analysis enables accurate mass measurement, rapid sequence confirmation, and localization of key post-translational modifications (PTMs) on protein subunits that are directly relevant to product quality.
In biopharmaceutical development, sequence variants (SV) are considered an inherent risk of producing complex proteins in living systems. Sequence variants are unintended changes to the amino acid sequence of a biotherapeutic and can be caused by errors in transcription or translation in the host cell, or cell culture and process conditions. Detailed analysis of SVs is important in process and product development to ensure the drug’s safety and efficacy. Even low‑level sequence variants can have significant implications for product quality, safety, and efficacy, making their accurate detection and characterization a critical requirement across development, process optimization, and regulatory submission.
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