Drug Development

Impurities

High-resolution, high-end multidisciplinary analytics for the highest patient’s safety.

Overview

Regulatory expectations driven by patient’s safety make API (Active Pharmaceutical Ingredients) and drug product impurity identification, quantification, and control a fundamental step in drug development. Impurity profiling during process development, optimization, and changeovers is an essential requirement to guarantee the quality of APIs and finished products.

The ICH Q3A guide classifies impurities in 3 groups: organic (starting materials, by-products, intermediates, transformation products, interaction products, degradation products, reagents, ligands and catalysts), inorganic (reagents, ligands, catalysts, heavy metals or residual metals, inorganic salts and other materials such as charcoal or filter aids) and solvent. Polymorphs and enantiomorphs are not considered in ICH Q3A, but represent another type of contaminant which require identification, quantification, and control. Impurity profiling includes identification,structure elucidationand quantitative determination of impurities and degradation products in drug materials and pharmaceutical formulations.

Chromatographic and spectroscopic techniques, either alone or in combination with other techniques are typically used for example LC-MS and GC-MS. Due to the quantitative nature of magnetic resonance impurity profiling and degradation studies (e.g. polysorbates) are performed directly enabling fast and easy testing without the need of response factor calculations, or the method redevelopment activities required by traditional LC methods, thereby saving time and reducing costs.

Structure elucidation of unknown impurities, degradants and force-degradation products are typically done by a combination of isolation/preparation step followed by NMR and MS data analysis. For an API dose at < 2 g/day, the organic impurities threshold is 0.1%. Any impurity above that threshold need to be identified. Once the structure is known the allowed threshold might increase to 0.5%, alleviating the pressure on the synthesis and purification steps. EPR spectroscopy shines light on otherwise unseen impurities such as free radicals and transition metals, which is of particular importance in forced-degradation (e.g. oxidation) studies and shelf-life determination. EPR is the only technique for the direct and non-invasive detection, identification, and quantification of paramagnetic impurities (organic free radicals and transition metals) at LODs down to parts per billion levels.

Heavy metal impurities can be identified, quantified, and monitored by X-ray fluorescence (TXRF, XRF) down to parts per billion levels. Both, USP and ICH establish (T)XRF as a tool to analyze heavy metals such as As, Hg, Co, V, Ni, and typical catalyzer elements such as like Pt, Pd, Rh, and V as detailed in USP 232, 233, 735, and ICH Q3D.

XRD directly probes the crystal structure and therefore enables detection and differentiation of different polymorphs. This allows control of and anticipation of polymorphic changes that may occur and adversely affect drug substance quality down to levels of ~0.1% weight percent.

相关产品

相关产品

D2 PHASER

D2 PHASER

Лучший в мире дифрактометр на скамейке. XRD для всех XRD для везде XRD для всего
D8 ADVANCE

D8 ADVANCE

Универсальный, простота в использовании чемпион предлагает лучшие в классе производительность на поликристаллического порошка и слоистых образцов.
S4 T-STAR TXRF spectrometer

S4 T-STAR

High-volume TXRF spectrometer for ultra-trace (sub-ppb) elemental analysis of very small sample amounts in the pg, ng or µg range: low operating cost, “green” technology
magnettech ESR5000

Magnettech ESR5000

The Magnettech ESR5000 is an innovative research instrument with high quality performance. It offers dedicated and tailored turn-key solutions for specific quality control, medical, and pharmaceutical R&D applications.
Ascend 400

Приборы ЯМР

ЯМР – неразрушающий метод анализа, позволяющий получать множество данных. Он дает подробную информацию о молекулярной структуре, динамических процессах и позволяет непосредственно наблюдать за химическими реакциями.
maXis II

maXis II

The latest in cutting-edge LC-Q-TOF MS technology provides enhanced resolution and mass precision for intact protein analysis, characterization of biopharmaceuticals, and native mass spectrometry analysis.

Поддержка

Labscape

Service & Life Cycle Support for Magnetic Resonance and Preclinical Imaging

Bruker’s commitment to provide customers with unparalleled help throughout the buying cycle, from initial inquiry to evaluation, installation, and the lifetime of the instrument is now characterized by the LabScape service concept.

LabScape Maintenance Agreements, On-Site On-Demand and Enhance Your Lab are designed to offer a new approach to maintenance and service for the modern laboratory