Professional Documents
Culture Documents
P har maceutical
S ciences
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
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
Reagents
Spectrofluorophotometers (RF)
Thermal analyzers
Property
analysis
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.
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)
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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
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.
,*
CLASS - Agent
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
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.
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).
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Pha r m aceut i c a l A p p l i c a t i o n s
Analysis Setting Window Labeled Nucleic Acid Quantitation – Detailed View Mode
(Measurement sample: OligoDNA labeled by Cy3 in TE buffer)
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olecule Analysis and Biotechnology
Pro t e i n A n aly s is
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
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Pha r m aceut i c a l A p p l i c a t i o n s
0.00
-0.25
0.0 2.5 5.0 7.5 10.0 12.5 15.0 17.5 20.0 min
I m ag i n g
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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
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
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
Without bypass
Standard solution
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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
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Pha r m aceut i c a l A p p l i c a t i o n s
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
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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.
Analytical
Surface
Sample Holder
Enteric film
Fig. 1 Fig. 2
17
Pha r m aceut i c a l A p p l i c a t i o n s
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.
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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
CT Image
of 4-Layer
Tablet
Transparent cover
Compression of Microcapsule
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Balances
Equipped with “Windows Equipped with next-
Direct Direct” (patent approved) Shimadzu's Electronic Balances and Scales generation mass sensor “UniBloc”
Direct
ELB
120 g to 12 kg
0.01 to 1 g
JQA-0376