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Pharmaceutical APIs, impurities
and primary reference standards
March 2017
detailed certificates of analysis • acknowledged by r
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LGC Quality - ISO 9001 • ISO/IEC 17025 • ISO Guide 34 • GMP/GLP • ISO 13485 • ISO/IEC 17043
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Introduction
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Contents
Introduction �������������������������������������������������������������������������������������������������������������������������������ii
Impurities ������������������������������������������������������������������������������������������������������������������������������A-1
Primary standards ����������������������������������������������������������������������������������������������������������������B-1
Email: [email protected] | Website: www.lgcstandards.com i
Introduction
Welcome to the new edition of our pharmaceutical impurities and primary reference
standards catalogue�
About LGC Standards
LGC Standards has successfully established a global reputation for the production of
impurities, primary reference standards and working standards, and as a single source for the
supply of pharmacopoeia reference materials� Our production site in Germany is accredited to
ISO/IEC 17025 and ISO Guide 34�
Our menu of custom services, including custom synthesis of impurities and metabolites,
characterisation, certification, packaging and distribution, adds value to the scientific support we
provide to our pharmaceutical customers�
Our relationships with the world’s leading pharmacopoeias and their range of Chemical
Reference Substances (CRS) and Reference Standards (RS), combined with in-house
production of certified reference materials and pharmaceutical impurities, enable us to meet
our customers’ specific needs. LGC is currently the exclusive distributor of ATCC cultures and
biological products throughout Europe and specified countries on the continent of Africa.
LGC Standards’ extensive network of sales offices and distribution centres means we offer
the widest range of reference materials from one single source for rapid delivery� Our staff can
provide scientific and technical guidance, including shipping and customs advice, in the local
language� Our range of products also includes reference materials for clinical and forensic
applications, phytochemicals, environmental analysis, physical properties determination,
and food and beverage analysis�
For more information about our range of services, or to receive any of our catalogues, please
refer to our website www.lgcstandards.com or contact your local office.
About LGC
LGC Standards is part of LGC� LGC, whose Science and Innovation division acts as
the designated UK National Measurement Institute (NMI) for Chemical and Biochemical
measurement, has a long history in the development and validation of analytical methods and the
production of reference materials�
Many of the analytical methods, which cover the food, environment, industrial, clinical and
pharmaceutical sectors, are accredited to ISO/IEC 17025 (Requirements for the competence of
testing and calibration laboratories)� Full details of the accreditation schedule can be found on the
UKAS website (www.ukas.com).
LGC’s Science and Innovation division is accredited to ISO Guide 34 (General requirements
for the competence of reference materials producers) for the production of (certified) reference
materials as is also our production site in Germany. The measurement capabilities used
to produce certified reference materials in its capacity as the UK NMI are verified through
participation on key comparison studies organised by the Consultative Committee for the
Amount of Substance (CCQM) of the International Weights and Measures Organisation (BIPM).
The certificates are recognised by other National Measurement Institutes, under the Mutual
Recognition Arrangement.
In its role as the NMI, LGC serves on the International Organisation for Standardisation (ISO)
Committee for Reference Materials (REMCO), which aims to carry out and encourage a broad
international effort for the harmonization, production and application of certified reference
materials (CRM)�
ii Email: [email protected] | Website: www.lgcstandards.com
About the catalogue
The first chapter of this catalogue comprises approximately 3,500 impurity and drug substance
reference standards produced by LGC. The second chapter includes a selected range of primary
reference standards which are produced under ISO Guide 34 and feature an even more detailed
certificate of analysis. They fulfill the official requirements for primary standards of organizations
such as the FDA, WHO and ICH.
Each product is accompanied by a detailed certificate of analysis (CofA), which gives information
on the identity and purity, together with the various analytical methods and their conditions�
Examples of our comprehensive certificates are shown at the beginning of the impurities and
primary standards sections�
Impurity standards
Impurities in a pharmaceutical substance can change the effects and side effects of a drug
significantly. Therefore, it is important to have an accurate detection of impurities.
The pharmacopoeial monographs regulate the legal definition but also the analysis and the
limits of impurities in a given substance. A wide range of known impurities is listed in individual
pharmacopoeial monographs. A great number, however, of these standards are not actually
available from the pharmacopoeias. The impurity standards produced by LGC serve to fill this
gap to a large extent.
The increasing importance of impurity reference materials is also becoming apparent in the
registration of drugs, where an exact identification and quantification of susceptible impurities is
required for an assured documentation�
Limits for impurities have been laid out in compendial monographs, in specifications from the
manufacturer internally or in the International Conference on Harmonisation (ICH) Guidelines
which have been agreed by Europe, Japan and the United States. The ICH has published four
guidelines on impurity issues:
ICH Q3A (R1): Impurities in New Drug Substances
ICH Q3B (R2): Impurities in New Drug Products
ICH Q3C (R5): Impurities: Guideline for Residual Solvents
ICH Q3D: Impurities: Guideline for Metal Impurities
The full wording of the ICH guidelines is available at the official website of the ICH: www.ich.org.
The ICH guidelines on impurities were originally developed for new, original drug substances
and products. However, it is now commonly agreed in the three ICH regions – by FDA, EMA and
Japanese regulation documents – that these guidelines need to be applied to generic compounds
as well, in addition to the pharmacopoeial monographs�
LGC impurity standards are thoroughly tested chemical reference substances and are used for
reliable identification and quantification of impurities in pharmaceutical ingredients and products.
They are also valuable tools for spiking experiments during validation studies of specificity and
accuracy of analytical methods�
The abbreviations EP, Pharmeuropa, BP and USP in the article description indicate that the
particular substance is mentioned as an impurity in that particular compendial publication�
They do not indicate that certain specification of reagents or drug substances mentioned in the
publications are fulfilled.
The standards – where they are actually listed as reagents or drug substances – may fulfill this
specification, but this is not the intention and is not certified on the CofA.
Email: [email protected] | Website: www.lgcstandards.com iii
Primary reference standards
Primary standards can be obtained from an officially recognized source, such as the
pharmacopoeias. However, when there is no official reference standard for a given purpose,
materials from other sources can be used. LGC Standards has produced and certified a new
range of primary standards that fulfill ICH’s, FDA’s and other regulatory bodies’ requirements for
pharmaceutical quality control�
Our primary standards are manufactured under ISO Guide 34 and come with the most detailed
certificate of analysis which includes identity checks by several qualitative techniques. Assay
information is provided by an accredited technique (qNMR whenever possible), and the assay is
confirmed by a second independent method (e.g. mass balance).
Controlled substances
A number of the pharmaceutical substances described in this catalogue, such as narcotics and
tranquillisers, are substances controlled by German legislation. You will find such substances
marked in the catalogue with a ‘CS’ in the corresponding column (after the column featuring the
CAS number).
The purchase, possession and use of controlled substances are subject to national and
international regulations designed to limit their abuse� It is the responsibility of the customer
to obtain any authorization necessary to both purchase and possess controlled substances,
complying with the laws of the importing country, before ordering�
Customers wishing to obtain controlled substances must contact their LGC Standards sales
office before ordering, and clarify with the sales specialists the relevant national requirements,
the associated charges and consequential delivery times. All orders for controlled substances
must be provided in writing and signed by an authorised person. The orders must be
accompanied with the original import permit and/or possession permit�
Use, safety and handling
Some pharmaceutical substances are toxic and require special handling. Virtually all
pharmaceutical reference substances have a pharmacological and/or biological activity� We
therefore recommend that all the products described in this catalogue should be handled as if
they were bio-active, toxic or infective, and that opened packs should only be handled by trained
laboratory personnel� We also strongly recommend to read the information provided by material
safety data sheets coming with our products�
All pharmaceutical reference substances and standards are for laboratory analytical use only and
not for use in humans�
How to buy from LGC Standards?
LGC is the most comprehensive source of reference materials, offering more than 100,000 for
online ordering at www�lgcstandards�com� Once registered, you will also be able to view pricing
and place orders. Alternatively, please feel free to contact our local offices worldwide for product
information and prices. All contact details are given on the back cover of this catalogue.
iv Email: [email protected] | Website: www.lgcstandards.com
General ordering information
The majority of products mentioned in this catalogue are available from stock; others may
have a delivery time of approximately four weeks. For substances marked with ‘request’ in the
column featuring the unit size, longer delivery times may apply� For custom synthesis, the time is
estimated from previous experience. Customers will be notified if unforeseen complications arise
during the synthesis. In the unlikely event that a synthesis does not reach the expected result,
LGC Standards reserves the right to cancel the order�
Please note that once delivered to the customer, reference substances are not returnable�
Customers requiring assistance with the purchase, use or application of a particular reference
substance should contact LGC Standards where technical staff are available to advise on the use
and suitability of the products�
Email: [email protected] | Website: www.lgcstandards.com v
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APIs and impurities
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Certificate of analysis - impurities reference materials
CERTIFICATE
Reference Substance
4-Methoxy-2-[[(5-methoxy-1H-benzimidazol-
2-yl)sulphonyl]methyl]-3,5-dimethylpyridine
1-Oxide (Omeprazole Sulphone N-Oxide)
O
NH
O
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O O N
O
Catalogue Number: MM0095.16
Lot Number: 15573
Molecular Formula: C17H19N3O5S Long-term Storage: 2 to 8 °C, dark
Molecular Weight: 377.42
CAS Number: [ 158812-85-2 ] Appearance: white solid
Melting Point: 185 °C (dec.)
Assay ‘as is’: 99.2 %
Date of shipment:
This certificate is valid for two years from the date of shipment provided
the substance is stored under the recommended conditions.
6 pages
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Certificate of analysis - impurities reference materials
I. Identity
The identity of the reference substance was established by following analyses.
Ia. 1H-NMR Spectrum
Conditions: 400 MHz, DMSO-d6
The structure is confirmed with the signals of the spectrum and their interpretation.
MM0095.16 lot number 15573 page 2/6
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Description:standards catalogue . About LGC Standards. LGC Standards has successfully established a global reputation for the production of impurities, primary reference standards and working standards, and as a single source for the supply of pharmacopoeia reference materials Our production site in
