Deutsche Akkreditierungsstelle GmbH Annex to the Accreditation Certificate D-RM-14176-01-00 according to the relevant clauses of ISO Guide 34: and DIN EN ISO/IEC 17025:2005 Period of validity: 11.01.2016 to 04.08.2019 date of issue: 11.01.2016 Holder of certificate: LGC GmbH Im Biotechnologiepark TGZ II, 14943 Luckenwalde Reference material producing in the fields: certified reference materials for organic neat compounds and salts thereof (e. g. pharmaceutically or forensically relevant substances); reference materials for organic neat compounds and salts thereof (e. g. pharmaceutically or forensically relevant substances); reference materials in form of solutions (e. g. pharmaceutically or forensically relevant substances) Abbreviations used: see last page The laboratory is permitted within the specified testing areas marked with *, without being required to inform and obtain prior approval from DAkkS: the modification, development and refinement of test methods. The listed test methods are exemplary. The laboratory maintains a current list of all test methods in a flexible scope of accreditation. This document is a translation. The definitive version is the original German annex to the accreditation certificate. 1/7
1 Certified reference materials for organic neat compounds and salts thereof (e. g. pharmaceutically or forensically relevant substances) Product Characteristic Range Pure Organic Substances Identity ----- Relative uncertainty in % ----- Method At least 4 of the following methods: FTIR-ATR, 1H NMR, 13C NMR, MS, melting point (capillary method, DSC), elemental analysis Assay > 95 % m/m 0,3 % Conformity of the test results within the limits of the measurement uncertainty of at least two methods: Titration, 100%-Method HPLC, 100%-Method DSC, carbon titration of the elemental analysis 2 Reference materials for organic neat compounds and salts thereof (e. g. pharmaceutically or forensically relevant substances) Product Characteristic Range Pure Organic Substances Relative uncertainty in % Identity ----- ----- Method Thorough identity checking by several of the following methods or comparison to an international accepted standard: FTIR-ATR, 1H NMR, 13C NMR, MS, melting point (capillary method, DSC), elementary analysis Assay > 90 % m/m < 2 % Assay detection by accredited absolute method or 100%- method (mass balance) with accredited (validated) testing methods Additional assay verification by an independent testing method Period of validity: 11.01.2016 to 04.08.2019 Translation 2/7
3 Reference materials in form of solutions of organic neat compounds and salts thereof (e. g. pharmaceutically or forensically relevant substances) Product Characteristic Range Method Solutions of pure organic substances Assay 0,005 10 g/l Gravimetric production with high precision weighing, on the basis of highly pure starting materials (characterised by quantitative analysis with accredited testing method like e.g. carbon titration of the elemental analysis, examined by 100% - impurities), verified by quantitative analysis (HPLC/GC) against external standard, contamination-free homogenisation and filling The determination of the reference values is based on the following test methods 1 Identity tests of organic compounds with melting point analysis (capillary method)* SOP 06-010 EXAMPLES Product LGCQUANT0123.00 2014-08-05 Product LGCQUANT1443.00 2014-08-05 Melting Point Identity test of solid, organic pure substances by melting point measurement (capillary method) Identity test of Ethinylestradiol Identity test of Brotizolam 2 Identity tests and assay determinations of organic compounds with elementary analysis * SOP 06-039 -11 SOP 06-039 -11 Elemental Analysis Determination of C-, H- and N-content of liquid and solid organic pure substances using elemental analysis for the test on identity Elemental Analysis Content determination of liquid and solid organic pure substances using carbon titration of the elemental analysis Period of validity: 11.01.2016 to 04.08.2019 Translation 3/7
3 Identity tests and purity determinations of organic compounds with spectroscopy * SOP 06-036 SOP 06-053 2011-12 IR Identity test of solid and liquid organic pure substances by infrared spectroscopy (FTIR-ATR) NMR Identity test of liquid and solid organic pure substances by 1H NMR spectroscopy and by 13C NMR spectroscopy 4 Purity and assay determinations of organic compounds with quantitative nuclear magnetic resonance (qnmr) * SOP 06-044 SOP 06-044 Quantitative NMR - Assay determination of solid and liquid organic pure substances Quantitative NMR Determination of residual solvent contents in pure organic compounds 5 Assay determinations of organic compounds with UV-Vis spectroscopy * SOP 06-029 2013-05 SOP 06-029, Annex 4 UV-Vis Spectrophotometry - Assay determination of organic substances Assay determination of ethanol in aqueous solution with UV/VIS Spectrophotometry via derivatisation with ADH and comparison to a standard 6 Identity tests and purity determinations of organic compounds with mass spectrometry* SOP 06-022 SOP 06-022, Annex 3 MS Identity test of solid and liquid organic pure substances by mass spectrometry (ESI) Determination of the degree of deuteration of organic compounds with HRMS 7 Purity determinations of organic compounds with gravimetry * SOP 06-037 2010-05 TGA Determination of residual solvent content of solid organic pure substances by thermal gravimetric analysis Period of validity: 11.01.2016 to 04.08.2019 Translation 4/7
SOP 06-035 -04 SOP 06-028 -11 LOD Determination of residual solvent content of solid organic pure substances by Loss On Drying (LOD) Sulfated Ash Determination of inorganic components in organic pure substances as limit test by Sulphated Ash in a microwave oven 8 Purity and assay determinations of organic compounds in solution with titration * SOP 06-006 SOP 06-024 Titration Assay determination of solid and liquid organic pure substances (in solution) by potentiometric titration KFT Determination of water content up to a content of 20% in solid and liquid organic pure substances by Karl-Fischer-Titration - Testing Procedure 9 Purity and assay determinations of organic compounds with gas chromatographie (GC)* SOP 06-073 2010-05 SOP 06-064 2011-02 EXAMPLES Product LGCAMP0078.07-11 2011-07-04 Product LGCAMP0420.00-01 2011-06-30 GCMS-Headspace Residual solvent content in wt% in organic pure substances Purity and assay determinations of organic compounds with GC-MS Purity determination of 7-Aminonitrazepam 1.0 mg/ml in Acetonitrile Purity determination of Chlorpromazine Hydrochloride 1.0 mg/ml in Methanol (as free base) Period of validity: 11.01.2016 to 04.08.2019 Translation 5/7
10 Purity and assay determinations of organic compounds with HPLC * SOP 06-032 2011-09 EXAMPLES Produkt LGCQUANT0431.00 2013-06-04 Produkt LGCQUANT0432.00 2013-09-10 HPLC Purity determination of solid and liquid organic pure substances by HPLC (HPLC with UV-Detector) - Testing Procedure Purity determination of Methyl Parahydroxybenzoate Purity determination of Propyl Parahydroxybenzoate 11 Identity tests and purity determinations of organic compounds with differential scanning calorimetry (DSC) * SOP 06-038 SOP 06-038 DSC Purity determination of solid, temperature-stable, organic pure substances with a content >98.5% by DSC Melting Point Identity test of solid organic pure substances by melting point measurement (DSC) Pertinent documents: SOP 06-011 SOP 06-027 SOP 06-031 2010-04 SOP 06-052 2010-05 Ph. Eur. 6.5 Chap. 2.2.34 Ph. Eur. 6.5 Chap. 2.5.32 Ph. Eur. 6.5 Chap. 2.3.32 Melting Point Identity test of solid organic pure substances by melting point measurement Method Development KFT - Determination of water content up to a content of 20% in solid and liquid organic pure substances by Karl-Fischer-Titration - Method Development HPLC Purity determination of solid and liquid organic pure substances by HPLC (HPLC with UV-Detector) Method Development HPLC Purity determination of solid and liquid organic pure substances by HPLC (HPLC with UV-Detector) - Method Validation Thermal Analysis - Thermogravimetry Microdetermination of water Coulometric Titration Loss on Drying Period of validity: 11.01.2016 to 04.08.2019 Translation 6/7
Ph. Eur. 6.5 Chap. 2.2.29 Ph. Eur. 6.5 Kap. 2.2.28 Ph. Eur. 6.5 Chap. 2.2.34 Ph. Eur. 6.5 Chap. 2.2.20 Ph. Eur. 6.5 Chap. 2.4.14 Ph. Eur. 6.5 Chap. 2.2.33 Ph. Eur. 7.2 Kap. 2.4.24 2011 Ph. Eur. 7.2 Kap. 2.2.25 2011 Ph. Eur. 6.5 Chap. 2.2.24 Ph. Eur. 6.5 Chap. 2.2.43 Ph. Eur. 6.5 Chap 2.2.14 Liquid Chromatography Gas Chromatography Thermal Analysis - DSC Potentiometric Titration Sulfated Ash NMR Spectroscopy Residual solvent per GC Headspace Absorption Spectrophotometry UV and Vis IR Spectroscopy Mass Spectrometry Melting Point Capillary Method Abbreviations used: DSC ESI FTIR-ATR GCMS HPLC NMR SOP Differential Scanning Calorimetry Electrospray-Ionisation Fourier Transform Infrared Spectroscopy Attenuated Total Reflectance Gas Chromatography-Mass Spectrometry High-Performance Liquid Chromatography Nuclear magnetic resonance Standard operation procedure at LGC GmbH Period of validity: 11.01.2016 to 04.08.2019 Translation 7/7