---

Characterisation of the metabolites of drug candidates is
a critical step in drug development. The observed activity
and toxicity of a drug molecule may be severely impacted
by metabolic modification.
Metabolites may show different pharmacological activities
to the parent including toxicity not seen with the parent
drug. Therefore, it is essential that metabolites can be found
and identified.
In this application brief, we demonstrate the use of
software-based metabolite prediction coupled with
high-performance Qq-TOF LC-MS and component-finding
algorithms for the discovery and identification
of metabolites of the well-known drug Verapamil.

---

The nano-Advance UHPLC system delivers exceptional
separations with a host of productivity enhancing features
to provide the very best nano UHPLC system. Ideally suited as a
key component of an LC-MS system, the nano-Advance UHPLC
dramatically increases MS productivity and utilization while
providing users with the flexibility and robustness needed for
the most demanding applications.

---

The use of DHAP as MALDI matrix enhances the formation
of multiple charged protein ions. These ions can be well
calibrated by protein standards such as myoglobin or
cytochrome c in the 8-20 kDa m/z range.
The ultrafleXtreme with FlashDetector in combination with
4GS/s digitization rate can turn externally calibrated high
quality data obtained from DHAP preparations into intact
protein molecular weight (MW) information at hitherto
unknown accuracy levels in the low ppm range.
Accurate intact molecular weight analysis adds an additional
characterization tool to the already considerable range of
biopharmaceutical characterization workflows which are
possible with Bruker MALDI-TOFs.

---

Rapid, Confident Characterization

Maximize your range of characterization techniques
with ultrafleXtreme™

• Rapid product confirmation
• In depth amino acid sequence coverage
• Accurate intact protein mass
• N/C-terminal sequencing
• PTM, truncation and mutation identification
• Glycan identification with quantitative assignment

---

Explore Your Applications with MALDI-TOF

The new ultrafleXtreme™ revolutionizes what you
can achieve with a MALDI-TOF and opens new fields
for research and industry.
Applications such as in-depth characterization of
Biopharmaceuticals, high speed tissue imaging based
biomarker discovery and glycoproteomics extend
beyond classical proteomics utilizing a multitude
of technology innovations and unique proprietary
software.

---

Metabolomics in Focus Welcome to the Daltonics Dispatch,
a resource from Bruker Daltonics
highlighting the application of mass
spectrometry technologies to provide
answers to analytical questions that
confront our customers everyday. At
Bruker Daltonics, we’re proud to be a
leader in providing Mass Spectrometry
solutions. We are committed to earning
our reputation for outstanding
performance, superior quality, and
excellent service and support. To that
end, we’ve developed the Dispatch as a
platform to illustrate, through short
papers and editorial pieces, how our
various mass spec technologies are
being applied to applications in
laboratories around the world. Each
issue will focus on an application area
and will be highlighted by examples of
how researchers are utilizing our mass
spectrometry systems to effectively
answer analytical questions. We’ve
created the Dispatch as a vehicle for
you to learn and benefit from the results
and experiences of others who
successfully overcame challenges.
We hope you will be inspired by their
success. This is your newsletter-so
please help us make it work for you!
E-mail us at dispatch@bdal.de. with
your ideas, submission, or comments
We hope you enjoy the Dispatch!

---

For the identification and especially the differentiation of
structural isomeric compounds MSn is often mandatory,
making ion trap systems the instrument of choice.
Here we present new developments implemented with
the amaZon speed system enabling fast and efficient MSn
analysis compatible with modern UHPLC and resulting in
reproducible, high quality fragmentation spectra .

---

In this study we profiled metabolite extracts of wild type
and mutant Arabidopsis thaliana seedlings impaired in
flavonoid biosynthesis. Multivariate data analysis revealed
that several compounds were absent in the mutant strains.
MS/MS and Pseudo-MS³ data acquired on a maXis impact
high-resolution Q-TOF instrument enabled unambiguous
elemental composition determination for precursor and
fragment ions.
Correlating this information with hypothetical compound
structures using the FragmentExplorer™ enabled the
tentative identification of a flavonoid-glucoside: quercetin-
3-O-rhamnoside-7-O-glucoside. The aglycon structure
could be verified by comparing Pseudo-MS³ spectra with
reference spectra of a quercetin standard. Interestingly,
querying an MS/MS library that was measured on a
micrOTOF-Q with the quercetin aglycon Pseudo-MS³
spectrum measured on the maXis impact returned
the same candidate hit. This result demonstrates the
applicability of shared MS/MS data acquired on different
Q-TOF instruments – even in different labs – for fast
de-replication workflows.

---

Because known pathogens become increasingly resistant
to antibiotics, and at the same time, new threats to human
health emerge, there is a constant need for the discovery
of novel natural products. Microorganisms have a longstanding
tradition as a source of biologically active small
molecules – termed “secondary metabolites“ – and in
addition to well-known producers like the actinomycetes,
new sources have been established.
We describe here the application of LC-MS and LC-NMR
techniques for the discovery and structural elucidation
of novel natural products from myxobacteria. These soilliving
bacteria exhibit outstanding biological characteristics
such as cooperative swarming on surfaces and formation
of multicellular fruiting bodies (Fig. 1). In addition, many
myxobacterial strains are also producers of secondary
metabolites exhibiting a wide range of biological activities
[1] – examples include the antibacterial thuggacins,
antifungal compounds like ambruticin and the cytotoxic
epothilones.