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C10G-E018A

P har maceutical
S ciences

Shimadzu Instruments Suppor ting


Research and Development
We provide suppor t in
a wide range of areas,
from dr ug discover y research
to quality control.

Research and Development


We are committed to providing a wide range of support that seamlessly covers diverse categories,
including the life science research products used in fields such as proteomics, genomics,
and metabolomics, chromatographs, mass spectrometers, and property testing machines.

Quality Control
We provide analytical instruments that meet the needs of the modern age by helping to
manufacture safe pharmaceuticals in compliance with IQ/OQ requirements and other
applicable regulations.

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Shimadzu Instruments Supporting
Pharmaceutical Sciences

Analytical research

discovery research
Life science drug

Discovery

Preclinical testing

Clinical testing

industrialization
Consideration of

Application

quality control
Manufacture and
Research department/
manufacturing process

Method development

genomics research
Proteomics and

Metabolomics research

Biomarkers

compounds
Synthesis of new

Screening

and toxicity testing


General pathology, safety,
kinetics and metabolism
Research of drug
efficacy and pharmacology
Research of drug

Formulation research

Phase1

Synthesis

Fermentation

Part 11 compliance*

IQ/OQ compliance*

Manufacturing processes

Quality control
Field of
Applicable equipment application
macromolecule analysis and biotechnology

MALDI-TOFMS instruments
Instruments supporting biological

MALDI plate spotters


Nanoflow high-performance
liquid chromatographs (nano LC)
Automated protein/peptide sequencing systems
Microchip electrophoresis systems
for DNA/RNA analysis
Spectrophotometers for life science

Reagents

Chemical inkjet printers for MALDI imaging analysis


(A l l types of sci enti fi c ana ly s is e qu ip me nt ar e a ppl i cabl e.)

High-performance liquid chromatograph ion-trap


time-of-flight mass spectrometers (LCMS-IT-TOF)
High-performance liquid chromatograph
mass spectrometers (LCMS)
High-performance liquid chromatographs (HPLC)

Ion chromatographs (IC)

Gas chromatographs (GC)

Gas chromatograph mass spectrometers (GCMS)


Constituent analysis instruments

Fourier transform infrared spectrophotometers (FTIR)

Spectrofluorophotometers (RF)

UV-VIS Spectrophotometers (UV)

Atomic absorption spectrophotometers (AA)

Multitype ICP emission spectrometers (ICP)

Electronic moisture balances (MOC)

Total organic carbon analyzers (TOC)

Electron probe micro analyzers (EPMA)


Energy dispersive X-ray fluorescence
spectrometers (EDX)
X-ray diffractometers (XRD)
instruments

Thermal analyzers
Property
analysis

Particle size analyzers

Strength testing machines ("Autograph")


Testing and
inspection
machines

Non-destructive inspection machines

Hardness and compression testing machines

Balances
*Some models do not support regulatory compliance. Contact your Shimadzu representative for details.
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Analytical Instruments Used in P
AXIMA Series MALDI-TOF mass spectrometers
PPSQ-31A/33A These sequencers cleave the N-
MALDI-TOF Mass Spectrometers perform soft ionization, making them
Automated Protein/Peptide terminal amino acids of proteins in
suitable for the ionization of a wide
Sequencing Systems order using Edman degradation,
range of samples, as it's possible to separate and detect the PTH-amino
obtain high-resolution, high-precision acids thus obtained with a high-
data quickly and easily. For this reason, performance liquid chromatograph,
they are used widely in fields involving perform identification with a PC used
synthetic macromolecules, such as life for system control and data processing,
science. and consequently determine the amino
acid sequence.

AccuSpot®
The AccuSpot MALDI plate spotter can
MALDI Plate Spotter
continuously spot eluate separated with
nano-LC or some other form of HPLC
onto MALDI-TOFMS target plates in
quantities no greater than a few
microliters.

CHIP-1000 This chemical inkjet printer dispenses


Chemical Inkjet Printer picoliter volumes of enzymes and
matrices onto parts of spots and tissue
sections of proteins plotted onto
membranes, making it possible to
directly prepare samples for MALDI-
TOF analysis and tissue imaging.

Life Science Drug Discovery


Reagent There are many different series of
reagent kits including “Ampdirect® Plus”, Metabolomics research
a gene-amplification reagent that allows Proteomics and genomics research
PCR to be performed without DNA
extraction, “Transdirect™ insect cell ”, a
cell-free protein synthesis reagent kit,
“13CNBS Stable Isotope Labeling Kit-N”,
a stable isotope labeling kit used for
quantitative proteomic analysis, and
“ORFinder®- NB Mass Sequencing Kit”,
a kit used to sequence the N-terminals
of proteins.
Cell-Free Protein Synthesis Reagent Kit

MCE-202 MultiNA This is a new electrophoresis platform BioSpec-nano This is a dedicated spectrophotometer
Microchip Electrophoresis used to perform DNA/RNA analysis Spectrophotometer for checking the concentration and purity
System for DNA/RNA Analysis using microchip technology. It cuts for Life Science of nucleic acid samples. It analyzes 1 to
analysis costs significantly, and allows 2 μL trace samples of nucleic acids.
the automated execution of up to 120 With automatic mounting and wiping
analyses. It provides powerful support functions, and easy-to-use software,
for assays of nucleic acid bases. it enhances analysis throughput.

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Pharmaceutical Development Proces
LCMS-IT-TOF This instrument can, while online with HPLC, obtain accurate mass information at high speed
High-Performance Liquid Chromatograph Ion-Trap Time-of-Flight Mass Spectrometer for MSn ions. It can also perform measurement based on high-speed ion polarity switching,
and obtain a wealth of information that is useful for structural analysis with a single sample
injection.

LCMS-2020 IG-1000
LCMS instruments combine the superior IG-1000 uses the induced grating (IG)
Urtra Fast Liquid Chromatograph Single Nano Particle Size Analyzer
separation capability of LC with the method, a new method developed by
Mass Spectrometer
qualitative analysis capability of MS. Using Shimadzu. It allows measurement of the
a mass spectrometer as the detector size of nanoparticles with high sensitivity
makes it possible to reduce both the and reproducibility.
analysis development time and analysis
time, and to streamline pretreatment. It
also gives a high level of detection
sensitivity and selectivity.

Preclinical Testing
General pathology, safety,
and toxicity testing
Research of drug kinetics and
metabolism
Research of drug efficacy and
pharmacology

 
Candidate Compound Discovery Formulation research

Biomarkers


  
  
Synthesis and discovery of new compounds
Screening



 

Prominence Series/LC-2010HT High-Performance Liquid Chromatograph (HPLC)

By separating and purifying the mixed liquid constituents of a pharmaceutical in a column


that is equilibrated with a liquid mobile phase, and then connecting various detectors in
order to reliably detect the peaks of the constituents, it is possible to perform the
fractionation, qualitative analysis, and quantitative analysis of the constituents precisely
and in a relatively short time. Centering on solvent delivery units (pumps) that allow mobile
phases to be delivered at rates in a range from the nano-order level to several mL/min or
more, this series features a varied lineup of products that can be used for a wide range of
applications, from research requiring microanalysis to quality control and large-scale
preparative purification. It is also possible to create various systems in accordance with the
target constituent, column size, and objective, from simple systems to ion chromatographs
and a variety of post-column/pre-column derivatization systems.

IRPrestige-21 By incorporating a high-sensitivity detector


UV-1800 This high-performance UV-VIS
Fourier Transform Infrared and a high-throughput optical element, this
UV-VIS Spectrophotometer spectrophotometer features a space-saving
Spectrophotometer spectrophotometer achieves an S/N ratio of design, and can be used as either a stand-
at least 40,000:1. The high-performance alone or PC-controlled instrument.
software includes an audit trail function, The main unit is USB-compatible, so
and security and log functions based on measurement data can be saved to USB
user names and passwords. memory and analyzed or printed using a PC.

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sses and Manufacturing
GC-2010 Plus This system performs the separation and GCMS-QP2010 Plus GCMS instruments combine the superior
High-End Capillary quantitative analysis of mixtures in which Gas Chromatograph separation of GC with the superior
Gas Chromatograph System gases such as helium are used as the Mass Spectrometer qualitative analysis of MS. Derivatization
mobile phase. It is employed widely in allows the high-sensitivity, high-separation
areas such as research and development analysis of low-molecular substances such
and quality control. It is used in various as amino acids and organic acids that are
processes to check the synthesis of difficult to analyze with LCMS.
compounds, check purity, and analyze
residual organic solvents.

Consideration of Commercialization
Synthesis
Fermentation

    


Clinical Testing
Phase1
   
Application
FDA CFR 21 Part 11
compliance

RF-5301PC With a bright optical system that uses a XRD-6000 By incorporating a high-precision, vertical-
Spectrofluorometer blazed holographic grating and digital X-ray Diffractometer type goniometer and Windows-compatible
signal processing, this instrument achieves software, this instrument achieves superior
an S/N ratio of at least 150:1. It supports multitasking operability. It is highly cost-
fluorescence/excitation/synchronous effective, and supports a wide range of
spectrum measurement, quantitative applications with a comprehensive selection
measurement, and time-course of options.
measurement.

ICPE-9000 This instrument offers both high throughput MOC-120H This instrument measures the percentage of
Multitype ICP Emission Spectrometer and easy analysis. The processing of large Electronic Moisture Balance moisture contained in a sample. The sample is
amounts of data, as required in the heated by infrared irradiation, and the moisture
selection of spectral lines, which was a percentage is obtained from the change in mass
problem with previous multitype ICP due to evaporation. This method is called “loss
instruments, is no longer an issue. The on drying”, and is used in many official standard
software includes various “assistant” measurement methods. This instrument
features that allow anybody to perform incorporates a quartz heater, which attains
accurate analyses in a short time. superior temperature distribution as well as a
long service life, the “UniBloc” aluminum integral
mass sensor, which offers outstanding
performance, as well as numerous functions.

AA-7000 This instrument is packed with functions, TOC-V The TOC-V series includes products using
Atomic Absorption Spectrophotometer including wizAArd functions that are easy Total Organic Carbon Analyzers the combustion catalytic oxidation method
to use even by analysts with little and the wet chemical oxidation method.
experience in atomic absorption, automatic They can also be used with the swab direct
switching between flame and furnace using combustion method when combined with a
a dual atomizer, 2-way background solid sample combustion unit. From
correction (D2 and SR methods), a inspections of the water used in drug
vibration sensor and gas leak detectors. manufacture to cleaning validation, these
TOC analyzers can be used widely in the
management of the total amount of organic
carbon in drug manufacturing processes.

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Instruments Supporting Biological Macromolecule Analysis and Biotechnology

Constituent Analysis Instruments

Property Analysis Instruments

Testing and Inspection Machines

Manufacture
Manufacturing processes
IQ/OQ compliance
DSC-60 Differential scanning calorimetry (DSC)
Quality control

 
Differential Scanning Calorimeter is listed as a general testing method in

     

Supplement 2 of the Japanese
Pharmacopoeia. This instrument makes
it possible to measure changes in the
amount of heat or temperature resulting
from melting or crystal transformation
that occurs when a sample is heated or
cooled. In the development and quality
control of pharmaceuticals, DSC is
used for the evaluation of crystal
polymorphs.

on
SALD-7101 This instrument is the first of its kind to
t 11 Nano Particle Size Analyzer incorporate a 375-nm-wavelength
ultraviolet semiconductor laser. It is a
revolutionary instrument capable of
continuously measuring changes in
particle sizes ranging from 10 to
300 μm at 1-second intervals. It can be
used to analyze and observe processes
involving the dispersion, aggregation,
and dissolution of nano-particles in real
time, and also supports the analysis of
high-concentration samples (20 wt%
max.) and extremely small quantities of
sample.

EPMA-1720 This analyzer enables the high- SMX-90CT Setting a sample on the rotating stage
Electron Probe Micro Analyzer sensitivity elemental analysis of “inspeXio” Benchtop Microfocus between the X-ray generator and the X-
samples at the micron level. The control X-ray CT System ray detector, capturing the fluoroscopic
system is completely digital, and a images formed by the X-rays from
revolutionary level of operability allows various angles, accumulating them, and
observation and analysis to be performing reconstruction calculation
performed with just a mouse and a makes it possible to obtain cross-
keyboard. Operation is also possible sectional images of the sample interior.
from a PC connected via a network. The rotating stage can be moved in a
The EPMA-1720 is equipped with a vertical direction and the stage position
high-performance CeB6 filament, can be adjusted, making it possible to
making it practical to perform analysis set the imaging range and resolution in
at the sub-micron level using EPMA. accordance with the purpose of
observation and analysis.

EDX-720 The main unit of this instrument is a


AG-X Series These strength testing machines can
Energy Dispersive X-ray tabletop type with a compact design. It
“Autograph” Strength measure the amount of compression
Fluorescence Spectrometer is equipped with a large sample
Testing Machines and bending of tablets and analyze
chamber with a fully automated tablet formation. They are driven by
opening and closing door system. It can motors, and can measure forces in the
be used to analyze various types of range of 0.02 to 10,000 N. Replacing
samples, such as solids, powders, the jigs that make contact with the
liquids, disks, and thin films. Expansion sample in accordance with the test
is also possible with 16/8 sample conditions makes it possible to perform
exchange, a vacuum/helium tests for various forces with a single
atmosphere, and 4-type collimator, and machine. Specialized software
observation using a CCD camera. (TRAPEZIUM X) can set the test
conditions, display graphs and results,
and create reports.
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Shimadzu’s Basic FDA-Compliance C
Shimadzu’s basic policy is to comprehensively achieve compliance with all products used in laboratories, including chromatographic analysis
instruments (e.g., HPLC, GC, GCMS, and LCMS instruments), optical analysis instruments (e.g., UV, FTIR, and AA instruments), total organic
carbon (TOC) analyzers, thermal analysis instruments, and balances.*
Basing our product development on CLASS-Agent Ver. 2, we provide products and technologies, including chromatographic instruments,
spectroscopic instruments, balances, TOC analyzers, and thermal analysis instruments, that support Part 11 compliance of the analysis data used
in laboratories. We support the networking of the analytical instruments required by customers, and we help to improve work efficiency and ensure
data reliability.
*Some models do not support compliance. Contact your Shimadzu representative for details.

S h i m a d z u Part 11 -C o mp lia n t Net work Syst ems Ensure Dat a Reliabili t y


b y M e e t i n g Se c u rity , A u d it T rail, and Int egrit y Requirement s
Agent Report Ensures Part 11 Compliance of Excel Comprehensive Support for Part 11 Compliance
Allows utilization of Excel, which is widely used in the Shimadzu provides comprehensive support, not only with products,
pharmaceutical industry. but also with the creation of system operation procedures and
control procedures.

I n t e g ra t e d M a n ag eme n t o f A n a lyt ical Dat a by CLASS- Agent


Server HPLC GC LCMS GCMS TOC Office
Integrated Data search,
Management of re-analysis, approval
Analytical Data and electronic
signature

,*
CLASS - Agent

Other vendor's Thermal analyzer AA UV FTIR Balance


instrument

H ow A g e n t Re p o r t A ch iev e s Par t 11 Compat ibilit y for Excel

STEP 1 STEP 2
Agent Database
Create Excel template Register to database Templates and data already registered in the
database are used for calculations. The results
are also saved in the database.

Excel template

Analysis results data


DB
Excel report

PDF report
Data from analyzers Automatic registration

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e Concept
F e a t u re s o f A g en t R ep o rts
Simple system creation Easier report generation
Report templates can be created quickly by re-using existing Excel Reports are generated automatically and simply by selecting
worksheets. Created templates are easily registered to the database analysis data and report templates registered in the CLASS-Agent
for secure management using the registration tool. This reduces the database. No manual input is required, saving effort for report
workload before the system can be operated after introduction. generation and checking.

Automatic generation of PDF files Automatic database registration


A PDF file is generated automatically at the same time an Excel Created reports are automatically saved in the database for secure
report file is created. The excellent portability of PDF files is storage. Required reports and analysis data can be easily found and
effective for electronic report transfer. recalled using the associated information that is automatically
registered simultaneously.

Electronic signature-compatible
Electronic signatures can be applied to reports using standard
functions of CLASS-Agent Manager.

C om p l i a n c e with IQ/OQ

In order to prepare for FDA inspections, when equipment is installed Shimadzu conducts the IQ
or re-installed after relocation, it is necessary to confirm that the and OQ of pharmaceutical-
installation environment and the equipment conform to related products, and it is
specifications, and that equipment performance satisfies the possible for personnel with
applicable standards. IQ (Installation Qualification) requires the authority to certify
verification of the equipment at the time of installation, which qualification to conduct
includes verification of the specifications of analytical instruments, IQ/OQ inspections at
software, attached documents, and the installation environment, and customers’ facilities and
proof that training has been given to customers. OQ (Operational leave inspection records in
Qualification) requires the verification of the functional performance the appropriate format (for
of equipment and software. value).

STEP 3 STEP 4 STEP 5 STEP 6


Automatic calculation,
Extract and select calculated data Select template automatic database registration Automatic report generation
(background processing)

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Pha r m aceut i c a l A p p l i c a t i o n s

Instruments Supporting Biological Macromol


Nu cl e i c A c i d A n a ly s is

Checking the Size of Nucleic Acids MCE-202 MultiNA


By incorporating a reusable microchip, we have achieved an analysis cost that is no greater Microchip Electrophoresis System
for DNA/RNA Analysis
than that of systems using agarose gel. The PCR fragment analysis and limited enzymatic
digestion-based fragment analysis of nucleic acid bases, which was prohibitively costly until
now, troublesome, and produced imprecise data because it was performed manually, can be
fully automated with quick, simple operations.

Data for Norovirus RT-PCR Products

Checking the Concentration of Nucleic Acids BioSpec-nano


In the experimental processes of gene expression analysis and DNA sequencing, the Spectrophotometer for Life Science
concentration of nucleic acid samples can be checked. In the simple nucleic acid quantitation
mode, the nucleic acid concentration and OD ratio are calculated, and in the labeled nucleic
acid quantitation mode, the labeled nucleic acid concentration, label concentration, labeling
ratio, and nucleotide concentration, etc. are calculated.
This spectrophotometer allows measurement even with minute sample amounts of 1 to 2 μL,
which makes it useful in various aspects of testing using biological samples.

Analysis Setting Window Labeled Nucleic Acid Quantitation – Detailed View Mode
(Measurement sample: OligoDNA labeled by Cy3 in TE buffer)

Enabling Simple, Quick PCR Ampdirect Plus


Ampdirect Plus (PCR buffer) suppresses the Gene-Amplification Reagent
action of the PCR inhibitors contained in
samples, and allows PCR to be performed on
samples containing blood, plant or animal
tissues, or SDS without DNA extraction.
Results obtained by performing PCR on a
mouse tail solution using Ampdirect Plus and
Nova Taq™ (recommended enzyme) are
shown here as an example. Simple, quick, low-
cost mouse genotyping is possible without DNA
extraction. Results of PCR Amplification of Mouse Tail Solution
Results almost the same as those obtained with DNA
extraction can be achieved simply by adding 0.5 μL of
mouse tail solution to the reaction solution.

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olecule Analysis and Biotechnology
Pro t e i n A n aly s is

Protein Identification AXIMA Performance


AXIMA Performance is a TOF-TOF- MALDI-TOF Mass Spectrometer
type MALDI-TOF mass spectrometer
equipped with high-energy CID. It
automatically performs PMF and
MS/MS ion searches and is capable
of high-efficiency, high-precision
identification. In applications
involving multiple samples,
combining it with a nanoflow liquid
chromatograph and a MALDI plate
Example of the Analysis of Phosphate Peptides
spotter helps increase efficiency.

Rapid Pretreatment for MALDI-TOFMS AccuSpot


Using HPLC to separate samples before analysis with MALDI-TOFMS enables the identification MALDI Plate Spotter
of minute samples with high precision and may help improve the peptide coverage used to find
more detailed differences in post-translational modification and other phenomena. Combining
these functionalities with AccuSpot makes it possible to construct a practical LC-MALDI system,
and thereby contributes to improvements in analysis/inspection efficiency.

Non-contact Spotting with AccuSpot

High-Sensitivity Peptide Analysis Prominence nano


Using the high level of basic performance 1 Nanoflow Liquid Chromatograph
1: m/z 464.26
2: m/z 526.60
offered by the LC-20ADnano solvent delivery
3: m/z 474.24
unit, which is equipped with a reflux flow control
system (patent pending), we have achieved a 0.192%RSD
retention time reproducibility of 0.20%RSD
max. (n = 6) at a flow rate of 300 nL/min. This 2

product is equipped with the simple-to-operate 0.088%RSD

specialized control software Nano-Assist, which


can be used with simple operations, and when 3

used in combination with an LCMS-IT-TOF 0.066%RSD

system equipped with a nano-ESI interface,


AccuSpot MALDI spotter, or a MALDI-TOF 0.0 5.0 10.0 15.0 20.0 25.0 30.0 35.0 40.0 45.0 50.0 55.0 min

mass spectrometer, it can produce highly Reproducibility for Products of BSA Enzymatic Digestion using
LCMS-IT-TOF (Retention Time Reproducibility for Major Peaks)
reliable data in proteome analysis. Flow rate: 300 nL/min

MS chromatograms based on the respective m/z


values are shown above.

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Pha r m aceut i c a l A p p l i c a t i o n s

Instruments Supporting Biological Macromolecule Analysis and Biotechnology


Pro t e i n A n a lys is

Determination of Amino Acid Sequences PPSQ-31A/33A


The N-terminal amino acids of proteins are Automated Protein/Peptide Sequencing Systems
mV PTH-AA 10 pmol
cleaved in order using Edman degradation, the 2.00
E
PTH-amino acids thus obtained are separated 1.75
NQ S T
D H
and detected with a high-performance liquid 1.50
G
chromatograph, identification is performed with 1.25 A
Y R
1.00
a PC used for system control and data MV K
0.75 P W
processing, and the amino acid sequence is 0.50
F I L

thereby determined. 0.25

0.00

-0.25
0.0 2.5 5.0 7.5 10.0 12.5 15.0 17.5 20.0 min

Example of the Analysis of PTH-Amino Acids

I m ag i n g

Identification of Proteins CHIP-1000


Using a chemical inkjet printer (CHIP-1000), it Chemical Inkjet Printer
is possible to dispense minute amounts of
enzymes and matrices onto tissue sections,
and perform MALDI-TOFMS, imaging analysis,
or profiling with an AXIMA-series product.

Entire Brain Region


Left: Example of Imaging MS Analysis Performed
with AXIMA
Right: Example of Dispensing of Matrix onto Tissue
Section with CHIP-1000

CHIP-1000 AXIMA Series

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Constituent Analysis Instruments
Superior Qualitative Analysis Capability Achieved with MS n LCMS-IT-TOF
High-speed, high-precision MSn measurement performed using LCMS-IT-TOF provides powerful support for High-Performance Liquid Chromatograph
the identification of target compounds, even in research fields such as impurity analysis, metabolite profiling,
Ion-Trap Time-of-Flight Mass Spectrometer
and biomarker discovery. In the example shown here, the ability to perform high-speed mass spectrum
measurement was utilized to obtain MSn data for four compounds eluted within a time interval of one minute
using the auto MSn function with the external standard method.
MS 1 HO
342.1691
N 4.09 ppm
O

OH
HO O
HO HO HO C 20H 23NO 4
N
N N N O
O O O
100 150 200 250 300 350 400 450 m/z
OH OH OH H3CO
O O HO HO
H3C
MS 2 324.1605
(x10,000,000) -1.54 ppm

1.00 Naloxone
Naltrexone
100 150 200 250 300 350 400 450 m/z
6-beta-naltrexol
Buprenorphine
MS 3
270.1137
0.50
-2.59 ppm

0.00 100 150 200 250 300 350 400 450 m/z

0.0 0.5 1.0 1.5 2.0


min

A Mass Spectrometer for a Wide Range of HPLC Applications LCMS-2020


Measurement results of components in blood plasma Ultra Fast Liquid Chromatograph Mass Spectrometer
using Co-Sense for BA System are shown here (direct
injection of blood plasma samples).
The chromatogram using a PDA (Photodiode Array)
detector shows small peaks; however, the MS
chromatogram demonstrates high-sensitivity detection of
those components.
In addition, in the PDA chromatogram, some peaks are
overlapped because of insufficient
separation, while this problem does not
occur with the MS measurement.

Data provided by Prof. Yamashita and Assistant Kataoka, Setsunan University.

A Formidable HPLC Instrument with Enhanced Functionality An Integrated HPLC Instrument with Enhanced Operability
This network-compatible HPLC instrument meets the With high-speed injection and the ability to
Prominence Series LC-2010HT
performance-related and functional requirements of handle microtiter plates, this integrated HPLC
High-Performance Liquid Chromatograph High-Performance Liquid Chromatograph
the modern age. It is the first HPLC in the world to instrument supports multiple-sample processing
incorporate remote internet-based control, and can and significantly improves analysis throughput.
perform sample injection in 10 s, the fastest time in Equipped with an auto-startup/shutdown
the world. It also offers the highest level of UV function and an auto-validation function, it
detection sensitivity in the world, is the first modular automates the work required for analysis and
system to support full automation, and achieves low- instrument management, and helps improve
contamination specifications with a widely-praised quality control and data productivity in factories.
sampling needle. In addition to the “LCsolution” It also incorporates advancements in basic LC
workstation, which has a well-established reputation performance with a temperature-control cell unit
for its operability, it can be controlled from a variety and low-contamination specifications.
of other companies’ workstations.

An HPLC Instrument that Achieves Ultra-high Speed and Ultra-high Resolution Prominence UFLC/UFLCXR
Prominence UFLC/UFLCXR is a revolutionary HPLC Ultra Fast Liquid Chromatograph
instrument that, in addition to inheriting the advanced
features of the Prominence HPLC series, such as low
contamination, high-sensitivity UV specifications, a
remote internet-based monitoring function, high
precision, and high stability, uses newly incorporated
technology to achieve both ultra fast analysis that does
not depend on high pressures and high-resolution
performance based on a column packed with ultrafine
particles.
Data Obtained with Ultra Fast Analysis of 7 Alkylphenones

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Pha r m aceut i c a l A p p l i c a t i o n s

Constituent Analysis Instruments


Efficient Purif ication of Natural Products LC-20AP
Scale-up from analytical to preparative LC is a critical 600
mV
Preparative HPLC System
1

factor in order to conserve solvent, and increase 500

efficiency and productivity of purification. 400

The LC-20AP pump contributes to a highly precise 300

scale-up workflow since it has excellent basic 200

performance over a wide flow range from analytical to 100

preparative flow rates. Preparative fractions can be 0

reanalyzed in analytical mode for trace impurities. 0 2.5 5.0 7.5 10.0 12.5 15.0 17.5 20.0 min
chromatographic condition
In addition to its basic performance, the LC-20AP Column: Shim-pack PREP-ODS(K)
30 mm i.d. × 250 mm L., 15 μm
Mobile phase and gradient:
provides substantial space and energy savings. The A; 50 mmol/L ammnoium formate buffer (pH3.7)
B; Acetonitrile
Shimadzu prep system can be utilized in applications 0 min -15 min: B 10% - 50%,
15 min -16 min; B 50% - 10%
ranging from purification of natural products to Flow rate: 30 mL/min
Detection: absorbance 240 nm
impurity analysis. Sample:
1:Swertiamarin
Purification of extract from Chinese herb,
Swertia japonica, using high flow rate gradient elution

Drug Quantitation Based on Direct Injection of Blood Plasma Prominence Co-Sense for BA
With unique sample pretreatment columns and a Biological Sample Analysis System
Sample: Blood plasma spiked with indomethacin
system configuration that applies column switching Sample injection solution (dilute solution):
Mixture of 0.1% aqueous phosphoric acid solution
technology, the Co-Sense for BA system allows and acetonitrile (95:5)
Dilution factor: 8
biological samples such as blood plasma and blood Detection: UV, 315 nm

serum to be injected directly for analysis. This makes


complicated pretreatment procedures unnecessary
and dramatically improves the efficiency of life science
research. With bypass

Without bypass

Standard solution

Comparative Data on the Recovery Rate Obtained with Indomethacin

A Pretreatment System Suited to LC-NMR/LC-MS Analysis Prominence Co-Sense for LC-NMR/LC-MS


Co-Sense for LC-NMR/LC-MS is an optimum system for the Automated Sample Pretreatment System
Work Flow with Co-Sense for LC-NMR for LC-NMR/LC-MS
structural analysis of impurities in pharmaceuticals, and is highly
effective for MS and NMR measurement in life science Rough Preparative Purification
Collection in sample loop
applications, such as research of the metabolism of living
organisms and the analysis of side reactions in chemical synthesis. Concentration and Desalination
Applying column switching technology to perform, automatically Each constituent is concentrated in the concentration column.
and online, the pretreatment procedures required for NMR and MS Desalination is performed by pumping purified water.
measurement, such as separation, concentration, and liquid
Solvent Replacement
replacement, eliminates the complex, troublesome, and costly work
Heavy water substitution is performed.
required with manual execution. Also, the separation of target
constituents using HPLC is not subject to the restrictions of NMR Elution
and MS, so HPLC parameters can be set with greater freedom. Elution performed with deuterated solvent.

Separation and Quantitation of Inorganic Anions and Cations Prominence HIC-SP/HIC-NS


The HIC-IP and HIC-NS are, respectively, suppressor-type and non- Ion Chromatograph
suppressor-type ion chromatography systems. They are widely used
to analyze the ionic constituents of samples in applications such as
the quality control of oral medications, eye-drops, and infusions,
and the management of the water used in manufacturing. Although
the main detection method is electrical conductivity, these systems
can be used with UV detectors. The high sensitivity of the
suppressor-type system (HIC-SP) and the high-resolution selectivity
of the non-suppressor system (HIC-NS) make it possible to handle a
wide range of applications, from samples with extremely low
concentrations to samples containing complex matrices with large
numbers of contaminant constituents. It is also possible to create a
dual-analysis system that can simultaneously analyze anions and Example of Batch Analysis of Inorganic Anions
cations.

14
Analysis of Residual Organic Solvents in Pharmaceuticals GC-2010 Plus
The headspace method is often used for the analysis High-End Capillary Gas Chromatograph System
of residual organic solvents in pharmaceuticals. This 2.00
(x100,000)μV

isoBuAc
method involves dissolving the pharmaceutical under

n-BuAc

isoAmOH
C5

isoPrAc

MiBK
nPrAc
MTBE
DEE
investigation in an appropriate solvent, enclosing the

C7
1.50

n-AmOH
EtOH
solution in a vial, heating the vial for a certain amount

EtAc
1.00

MeAc
of time, and then analyzing the volatile components in

n-BuOH
isoBuOH
MEK
the gaseous phase of the contents of the vial. For

Actn

n-PrOH
0.50

IPA
analysis performed under conditions specified, for
example, by a pharmacopoeia, the GC-2010 Plus is 0.00

ideal as it allows flow rate conditions, such as the split 5.0 10.0 15.0 20.0 25.0 30.0 35.0 40.0 min

ratio, to be set easily. Example of the Analysis of an Aqueous Solution of


Residual Organic Solvents (Specified as Class 3 by
ICH Guidelines) Using Headspace GC

Similarity Searches Suited to Qualitative Analysis of Metabolites GCMS-QP2010 Plus


In the example shown here, GCMS was used to analyze a TMS- Gas Chromatograph Mass Spectrometer
derivatized organic acid in urine. There is a high level of
similarity among the mass spectra of TMS-derivatized organic
acids; performing a database search based only on mass
spectra gives over 70 candidate compounds. With Shimadzu’s
metabolite database, it is possible to perform similarity searches
using retention indices. In situations where there are many
similar mass spectra and it is difficult to identify the target
compound, narrowing the search range using retention indices
search on mass spectrum alone.
reduces the number of candidate compounds and increases the
reliability of search results. Even in cases involving TMS
derivatization, performing a similarity search using retention Narrowing the search on retention index and mass spectrum.
search range using
indices makes it possible to narrow the range down to just one retention indices.
candidate compound. Urine Sample (Example of the Analysis of a
TMS-Derivatized Organic Acid)

Constituent Analysis of Powder Samples Possible without Pretreatment IRPrestige-21


If an accessory is used to perform single-reflection Fourier Transform Infrared Spectrophotometer
ATR with a diamond prism, infrared spectra can be
obtained for powder samples without pretreatment
simply by pressing the sample against the prism. Even
in the case of hydrochlorides such as
diphenylhydramine hydrochloride, infrared spectra can
be obtained without considering the possibility of ion
exchange with the matrix, which is a concern when the
pellet method is used.

Analysis of Diphenylhydramine Hydrochloride

Purity Tests Complying with the Japanese Pharmacopoeia


UV-1800
In the Japanese Pharmacopoeia, ultraviolet-visible
UV-VIS Spectrophotometer
spectrophotometry is specified as a method used to test
the purity of ethanol. It is specified that, in measurement
performed using a cell with an optical path length of
1 cm, the absorbances at 240 nm, between 250 and
260 nm, and between 270 and 340 nm must not exceed
0.40, 0.30, and 0.10, respectively, and that, in
measurement using a cell with an optical path length of
5 cm and using water as a blank, there must be no
peaks between 235 and 340 nm. Results obtained by
analyzing ethanol using a cell with an optical path
length of 1 cm are shown here as an example.
Analysis of Ethanol

15
Pha r m aceut i c a l A p p l i c a t i o n s

Constituent Analysis Instruments


Heavy Metal Analysis in Pharmaceutical Products AA-7000
Atomic absorption spectrophotometry is used for Atomic Absorption Spectrophotometer
heavy metal analysis in pharmaceutical products.
Applications include the analysis of lead in sucrose
used in coatings of tablets (purity measurement),
the analysis of cadmium and lead performed as a test
for containers and packing materials. Results obtained
by analyzing lead in sucrose used in coatings of
tablets by the furnace method are shown here as an
example.

Example of the Analysis of Lead in Sucrose Using a Furnace

An ICP Instrument that Enables Simultaneous Multi-Element Analysis ICPE-9000


Many gastrointestinal drugs use Multitype ICP Emission Spectrometer
Calibration Curve for Magnesium Calibration Curve for Aluminum
magnesium and aluminum as
constituents that protect the
stomach lining and suppress the
production of acid. Results
obtained by analyzing inorganic
elements using an ICP emission
spectrometer are shown here as an
Analysis Results
example.
Sample Mass Na Mg Al Ca Cu
A 1.40 g/pack 1.15 57.57 25.71 1.16 <0.004
B 1.43 g/pack 3.69 39.03 84.95 0.66 <0.004
C 1.20 g/pack 64.19 18.57 6.58 11.92 <0.004
D 1.30 g/pack 24.57 20.78 34.19 1.07 <0.004
E 1.15 g/pack <0.02 73.6 45.17 0.83 0.65
Units: mn/pack

Moisture Measurement of Samples MOC-120H


Measurement results obtained for sodium tartrate, Electronic Moisture Balance
which is used as a food additive, are shown here. Windows Direct
18
Although this measurement was performed using the
16
timed ending mode, there are nine modes, including
14
Moisture Content (%)

automatic ending mode, rapid drying mode, and step


12
drying mode, that can be used in accordance with the
10
sample. This instrument is also equipped with a bar
8
graph display that indicates the state of moisture
6
evaporation and a Windows Direct function (no
4
software required) that allows data to be uploaded to a
2
PC.
0
0 2.5 5 7.5 10
Time (min) Code:0042

Measurement of Sodium Tartrate

Management of Water Used in Pharmaceuticals TOC-V


Wet oxidation enables high-sensitivity measurement with a limit of Total Organic Carbon Analyzers
detection of 0.5 μg/L. This means that measurement is possible Swab sampling Transfer to sample boat

even for the increasingly pure water that is used in pharmaceuticals.

Cleaning Validation
Combining these analyzers with a solid sample combustion unit
enables measurement using the swab direct combustion method.
Water-insoluble contaminants that are difficult to detect with the TOC measurement
rinse method or the swab solvent extraction method can be
detected with high sensitivity.

Part 11 Compliance
Combining these analyzers with CLASS-Agent database total
management software makes it possible to meet Part 11
requirements. Use of Swab Direct Combustion Method in GMP Cleaning Validation

16
Simple Elemental Analysis without Pretreatment EDX-720
Cold medicines contain chlorine and bromine, which are relatively difficult to analyze using wet analysis. In Energy Dispersive X-ray
such cases, EDX instruments, which allow analysis to be performed simply without pretreatment, are effective Fluorescence Spectrometer
for production control. Results obtained by analyzing tablets sold as cold medicine are shown here.

Sample Pressure-Sensitive Tape

Analytical
Surface
Sample Holder

Example of Sample Setting Position

Qualitative Analysis of Cold Medicine

Elemental Distribution Analysis of Surfaces EPMA-1720


"N" analysis is an effective way of investigating the distribution of drug substances in pharmaceutical Electron Probe Micro Analyzer
preparations. In the example shown here, the analysis sample was an indole-based antihypertensive drug
with the kind of structure shown in Fig. 1. It is a controlled-release preparation in which the drug substances
are contained in a hydrophobic matrix. The "N" distribution revealed that the drug substance particles were
distributed fairly evenly in the matrix.

Enteric film

Matrix components Drug substance


Secondary electron image N distribution image

Fig. 1 Fig. 2

An XRD Instrument Offering Ease of Use and Multiple Functions XRD-6000


Analysis using X-ray diffractometers is indispensable for the quality control of chemicals. In addition to the X-ray Diffractometer
control of raw materials, there has recently been an increase in demand for the control of finished articles.
Analysis results obtained using the polycapillary parallel-beam method are shown here as an example.

Ranitidine Tablets Crystal Polymorph Measurement Data for Ranitidine Tablets

17
Pha r m aceut i c a l A p p l i c a t i o n s

Property Analysis Instruments


Evaluation of Co-existing Crystals DSC-60
If there are crystal polymorphs present in a Differential Scanning Calorimeter
pharmaceutical compound, they can affect the
efficacy; consequently the evaluation of crystal
polymorphs is an important aspect in the
pharmaceutical field. Such crystal polymorphs
can be easily analyzed with differential
scanning calorimetry (DSC). In the figure,
peaks corresponding to endothermal reactions
can be observed at 168.3°C and 202.2°C. By
observing the state of the sample and
performing DSC at the same time, it was
possible to ascertain that both of these peaks DSC of Sulfathiazole
occurred because of melting and that there
were different types of crystal polymorphs in
the sulfathiazole sample.

Evaluation of the Dispersion, Aggregation, and Dissolution of Particles in Medicine and Biotechnology
The SALD-7101 seamlessly covers a measuring range of 10 nm to 300 μm. In addition to
primary nanoparticles, it can simultaneously perform the real-time analysis of aggregates and SALD-7101
contaminants with dimensions of several μm or more. Results obtained by using the SALD- Nano Particle Size Analyzer
7101 to evaluate the dispersibility of liposomes, which are used in drug delivery systems
(DDS), are shown in the figure. The existence of aggregates that may influence permeability
with respect to blood vessels and blood vessel walls is captured clearly.

Evaluation of the Dispersibility of Liposomes

Evaluation of Fullerene Hydroxide IG-1000


Photodynamic therapy (PDT) is a medical technology effective for the treatment of cancer. It Single Nano Particle Size Analyzer
works by administering a photosensitizer to a patient's cancerous tissue and then exposing the
photosensitizer to light. Fullerene hydroxide has an extremely small particle size of 1 nm and is
highly anticipated as this photosensitizer. The particle size of fullerene hydroxide cannot be
measured by conventional measurement methods using scattered light. The IG-1000, however,
adopts the "Induced Grating (IG) Method," a revolutionary new method unique to Shimadzu.
This method enables the particle size of fullerene hydroxide to be measured with high
sensitivity and high reproducibility, thus allowing the dispersity of photosensitizer particles to be
measured, which is important for the practical application of fullerene hydroxide.
Particle Size Distribution (Volumetric Basis)
Normalized Particle Amount

Measurement Results of Fullerene


Hydroxide Using IG-1000
(Sample provided by Prof. Kokubo of
Particle Diameter (nm) Osaka University)

18
Testing and Inspection Machines
Strength Tests of Tablet Splitting for Infant Use AG-X Series
In general, tablets intended for adults “Autograph” Strength Testing Machines
are split in two in order to allow use by
infants. Using the AG-X series to
perform three-point bending tests and
cantilever bending tests makes it Tablet
possible to optimize the depth of the
groove in the tablet surface that allows
it to be split accurately.

Test Conditions
Distance between lower supporting points: 8 mm
Test speed: 2 mm/min Three-point Bending Test of Tablet

Internal Observation of Tablets SMX-90CT


This desktop-size X-ray CT scanner is ideal for the
“inspeXio” Tabletop Microfocus X-ray CT System
non-destructive inspection and internal structural Tablet
observation of pharmaceuticals, living organisms, and
bones. Simply setting and positioning the sample is all
that is required to start immediate CT imaging. It uses
a flat panel detector (FPD), which makes it easy to
obtain extremely clear cross-sectional images without
distortion or unevenness.
Aluminum
foil

CT Image
of 4-Layer
Tablet

Transparent cover

Hardness Tests of Coating Layers DUH-211/211S


The DUH instruments can measure the Dynamic Ultra Micro Hardness Testers
hardness and strength of a sample by
pushing an indenter into the sample and
performing calculations on the
corresponding test force and indentation
depth. This makes it possible to evaluate
the characteristics of miniaturized,
streamlined coating materials.

Test Results for Coating Layer

Compression Strength Evaluation of Microcapsules MCT-211 Series


This series is ideal for evaluating the compression
Micro Compression Testing Machines
characteristics of microscopic materials, such as
particulate objects and microcapsules. It enables
particle-by-particle evaluation of the dispersion force
applied to primary particles in response to the
application of external force to particulate objects and
the strength of the film layers of microcapsules.

Compression of Microcapsule

19
Balances
Equipped with “Windows Equipped with next-
Direct Direct” (patent approved) Shimadzu's Electronic Balances and Scales generation mass sensor “UniBloc”

AU Series UW/UX Amidia BL BW/BX-K


42 to 320 g 220 to 8,200 g 220 to 3,200 g 12 to 52 kg
0.01 to 0.1 mg 0.001 to 0.1 g
TW/TX/TXB 0.001 to 0.1 g 0.1 to 1 g
220 to 6,200 g
0.001 to 1 g
Direct Direct Direct

Direct

ELB
120 g to 12 kg
0.01 to 1 g

JQA-0376

Founded in 1875, Shimadzu Corporation, a leader in the


development of advanced technologies, has a distinguished
history of innovation built on the foundation of contributing to
society through science and technology. We maintain a global
network of sales, service, technical support and applications
centers on six continents, and have established long-term
relationships with a host of highly trained distributors located
in over 100 countries. For information about Shimadzu, and to
contact your local office, please visit our Web site at
www.shimadzu.com

SHIMADZU CORPORATION. International Marketing Division


3. Kanda-Nishikicho 1-chome, Chiyoda-ku, Tokyo 101-8448, Japan
Phone: 81(3)3219-5641 Fax. 81(3)3219-5710
URL http://www.shimadzu.com

MCE®-202 MultiNA is not available in the United States.


The contents of this brochure are subject to change without notice.

Printed in Japan 2330-02001-20A-NS

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