Creative BioMart Chromatography provides GTI analysis services include method development, validation, analysis and transfer for genotoxic impurities in starting materials, intermediates, APIs and/or drug products. Genotoxic impurities (GTI) refers to a substance that can directly or indirectly cause DNA damage and can induce gene mutation or chromosome mutation at very low concentrations, with a potential carcinogenic tendency. Many authoritative organizations such as FDA, ICH and USP have issued guidelines clearly defining the limits of GTIs. GTIs may be introduced as starting materials and reagents, or synthesized in the form of an intermediate or reaction by-product (Fig. 1). The thorough study of GTIs would be one of the most important aspects and requirements in the manufacturing process of pharmaceuticals. By preparing chromatography and other techniques, the GTIs can be quickly separated, and then the qualitative, quantitative and safety studies can be carried out. Our GTI analysis is carefully following the ICH guidelines to apply a range of highly specific and sensitive techniques. Our solutions include but are not limited to LC-MS, LC-MS/MS, UPLC, HPLC, HPLC-UV, GC, GC-MS, GC-FID, GC-ECD, etc.
Fig. 1 Simulated synthetic route: potential sources of genotoxic impurities include starting materials, reagents, intermediates, side reactions, impurities. (Pierson D. A., et al, 2009)
GTI Analysis Techniques
| Type | Name | CAS No. | Methods | Limits |
|---|---|---|---|---|
| Sulfonates | Methyl methanesulfonate | 66-27-3 | GC-FID | 0.01% (headspace injection); 0.4ppm, 15ppm (direct injection) |
| Ethyl methanesulfonate | 62-50-0 | GC-FID | 15ppm, 0.01% (headspace injection); 0.4ppm (direct injection) | |
| Methyl p-toluenesulfonate (PTSM) | 80-48-8 | HPLC-UV | 15ppm | |
| GC-FID | 2ppm | |||
| Ethyl p-toluenesulfonate | 80-40-0 | HPLC-UV | 15ppm | |
| GC-FID | 2ppm | |||
| Isopropyl 4-toluene sulphonate | 2307-69-9 | HPLC-UV | 15ppm | |
| GC-FID | 2ppm | |||
| Ethyl benzenesulphonate | 515-46-8 | HPLC-UV | 0.1% | |
| Methyl benzenesulfonate | 80-18-2 | HPLC-UV | 0.1% | |
| Haloalkanes | 2-Bromopropane | 75-26-3 | GC-FID | 15ppm (headspace injection) |
| 1-Iodopropane | 107-08-4 | GC-FID | 8ppm (direct injection) | |
| Iodomethane | 74-88-4 | GC-FID | 37.5ppm (direct injection) | |
| 1-Chloro-3-(N,N-dimethyl)aminopropanehydrochloride | 5407-04-5 | GC-FID | 37.5ppm (direct injection) | |
| Bromoacetic acid | 79-08-3 | AEX | 0.01% | |
| 1-Chlorohexane | 544-10-5 | GC-MS | 4ppm | |
| 2-Chlorohexane | 638-28-8 | GC-MS | 4ppm | |
| 3-Chlorohexane | 2346-81-8 | GC-MS | 4ppm | |
| 2,3-Dichloro-1-propanol | 616-23-9 | GC-MS | 5ppm | |
| 1,3-Dichloro-2-propanol | 96-23-1 | GC-MS | 5ppm | |
| 1,2,3-Trichloropropane | 96-18-4 | GC-MS | 2ppm | |
| 3-Ethoxy-1-chloro-2-propanol | 4151-98-8 | GC-MS | 5ppm | |
| Epichlorohydrin | 106-89-8 | GC-MS | 5ppm | |
| Methyl bromoacetate | 96-32-2 | GC-ECD | 0.01% | |
| Isopropyl bromoacetate | 29921-57-1 | GC-ECD | 0.01% | |
| Acid Halides | Chloro-formicacihexylester | 6092-54-2 | GC-FID | 4ppm |
| 4-Chlorobutyryl chloride | 4635-59-0 | GC-FID | 8ppm | |
| Acetyl chloride | 75-36-5 | GC-FID | 0.075% | |
| Ethyl oxalyl monochloride | 4755-77-5 | HPLC-UV | 15ppm | |
| Carbamates | EthanediaMide iMpurity A | 1210348-34-7 | HPLC-UV | 15ppm |
| 4-d]thiazole-5-carboxylic acid | 365998-36-3 | HPLC-UV | 15ppm | |
| Edoxaban Impurity 16 | 480450-69-9 | HPLC-UV | 15ppm | |
| Aromatic Amines | 2-amino-6-aza-6-methyl-4,5,6,7-tetrahydrobenzothiazole | 17899-48-8 | HPLC-UV | 15ppm |
| 2-Amino-5-chloropyridine | 1072-98-6 | HPLC-UV | 15ppm | |
| 4-(4-aMinophenyl) Morpholinone | 438056-69-0 | HPLC-UV | 75ppm | |
| (S)-3-(4-aMinophenoxy)propane-1,2-diol | 58754-71-5 | LC-MS | 5ppm | |
| 1,3-Bis(4-nitrophenoxy)-2-propanol | 65911-02-6 | LC-MS | 5ppm | |
| 3-(4-nitrophenoxy)propane-1 | 34211-48-8 | LC-MS | 5ppm | |
| Others | Hexamethylphosphoramide | 680-31-9 | LC-MS | 4ppm |
| 1-Ethyl-3(3-dimethylamino)urea | 32897-26-0 | HPLC-MS | 15ppm | |
| 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride | 25952-53-8 | LC-MS | 15ppm | |
| Methylamine | 74-89-5 | GC-FID | 75ppm (headspace injection) | |
| … | … | … | … | … |
Our Specialty
- The technical team is experienced in testing and arranges the experiments in a timely and rigorous manner.
- A wide range of chromatography techniques (HPLC, UPLC, GC) and detection technologies to meet the requirements of different types of compounds.
- End-to-end services with high quality and fast turnaround time to ensure accurate and reliable analytical data.
- Perfect and thoughtful pre-sales and after-sales service, and timely solve customers' questions.
Creative BioMart Chromatography is equipped with a professional technical team to focus on the literature research, method development and verification of GTIs, so as to develop suitable chromatography-related methods for various GTIs of different chemical properties, for the achievement of appropriate detection limits. We have developed and validated analytical methods for various types of GTIs such as sulfonates, haloalkanes, acid halides, carbamates and aromatic amines, in compliance with different national regulations requirements. We also provide custom services to meet the customer’s special needs. Our customers have direct access to our experts and give timely feedback to any online inquiries. If you are interested in our services, please contact us.
How to Place an Order
*If your organization requires the signing of a confidentiality agreement, please contact us by email.
Reference:
- Pierson D. A., et al. (2009). Approaches to Assessment, Testing Decisions, and Analytical Determination of Genotoxic Impurities in Drug Substances. Organic Process Research & Development, 13(2), 285-291.
For Research Use Only. Not intended for any clinical use. No products from Creative BioMart may be resold, modified for resale or used to manufacture commercial products without prior written approval from Creative BioMart.