Antiviral Drug Impurity Profiling
The identification, quantification and control of impurities in drug products by regulatory authorities is a fundamental step in drug development due to patient safety concerns. Impurity profiling during the process development and optimization is an essential requirement to ensure the quality of the final product. Therefore, under the strict regulatory conditions for antiviral drugs, impurity profiling of drug products is a very critical task in the pharmaceutical industry. The presence of unknown impurities, unwanted solvents, even at very low levels, may change the effect of the drug efficiency and cause side effects. Therefore, impurity profiling of antiviral drug products using stability-indicative analytical methods has become critical.
BOC Sciences has introduced sophisticated chromatographic, spectroscopic and coupling techniques to establish a general scheme for estimating impurities in multiple antiviral drugs. Our analysis labs support the use of a variety of chromatographic methods such as thin layer chromatography (TLC), gas chromatography (GC), analytical and preparative high performance liquid chromatography (HPLC), spectroscopic methods such as mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy, and coupling techniques (HPLC/diode array UV, GC/MS and HPLC/MS). For example, in our previous antiviral drug impurity profiling projects, our experts identified impurities in propidium (4-[diethylcarbamoyl(methoxy)]-3-methoxy phenylglyoxylate, II) and two unsaturated impurities in allyl alcohol by GC/MS and HPLC/diode array UV, as well as by HPLC/MS and HPLC/diode array UV to estimate the impurity profile of Macipromone. Our impurity antiviral drug impurity profiling services include the identification, structural elucidation and quantitative determination of impurities and degradation products in drug materials and drug formulations.
Figure 1. An overview of impurity profile. (Pannala, R. 2019)
Impurities Classification
- Organic substances, such as starting materials, by-products, intermediates, transformation products, interaction products, degradation products, reagents, ligands and catalysts
- Inorganic materials including reagents, ligands, catalysts, heavy or residual metals, inorganic salts and other materials such as charcoal or filter aids
- Solvents
Impurity Profiling Services
- We employ chromatographic and spectroscopic techniques such as LC-MS and GC-MS for direct impurity profiling and degradation studies (e.g. polysorbate) for fast and simple testing
- At BOC Sciences, structural elucidation of unknown impurities, degradants and force-degradation products in antiviral drugs usually requires isolation/preparation process followed by NMR and mass spectrometry data analysis. For an API at doses less than 2 g/day, the threshold for organic impurities is 0.1%. Any impurities above this threshold need to be identified
- For heavy metal impurities such as As, Hg, Co, V, Ni, and typically catalyst elements such as Pt, Pd, Rh and V in antiviral drugs, we offer X-ray fluorescence (TXRF, XRF) techniques for identification, quantification and monitoring
- We support XRD for the detection of crystal structures, and are able to detect and differentiate of different polycrystals. This allows control and prediction of polycrystalline changes that may occur and adversely affect the quality of the drug
Figure 2. Overview of elemental impurities which are identified using ICP, ICP-MS. (Pannala, R. 2019)
Our Impurity Profiling Procedure
- We apply data management software and tools to track and manage impurities at each step of the synthesis route. Our team of experts modifies the analytical methods based on the specifics of the impurities. For example, LC/MS mehtod can be used as a complement to HPLC to obtain the mass spectrum for each impurity of interest
- Then, our analytical chemists and process chemists employ high-resolution mass spectrometry (HRMS) to screen the structural quantities of impurities relevant to the reaction. To further confirm the impurity structures, impurities are separated by preparative HPLC or SFC to obtain sufficient quantities of impurities for NMR analysis
- Finally, the impurity structures obtained from the above process will be cross-checked by synthesizing potential impurities using an orthogonal structure confirmation method. This initiative will add credibility to the impurity structures and is often requested as part of our clients' new drug applications. In addition, our synthesis laboratory can support the gram-level synthesis of each impurity for Good Laboratory Practice (GLP) toxicity identification
Why Partner with BOC Sciences?
- We apply our years of proven expertise and experience in antiviral drug development to improve the success of your program
- Our continuously updated facilities support a range of antiviral drug analysis and manufacturing services
- BOC Sciences' experienced team of scientists and regulatory staffs are focused on working with our clients to deliver timely and high-quality small molecule antiviral drugs
- Our partnerships with leading experts in emerging technologies allow us to apply innovative solutions to your antiviral drug research programs
Reference
- Pannala, R. Impurity Profiling of Solid Oral Drug Products to Sail through GDUFA-II Requirements.American Journal of Analytical Chemistry. 2018. 9: 187-209.
※ Please kindly note that our services are for research use only.
