The traditional method of toxicology evaluation is mainly in vivo animal experiments, utilizing rodents and non-rodents for bioassays at different time periods. Although this method has played an important role in the practical application of evaluating the potential hazards of drugs to human beings, its limitations have been gradually revealed with the development of science and technology. In vitro toxicological evaluation is being increasingly researched and applied as an alternative to traditional toxicological evaluation in animal models. Under limited conditions, the results of in vitro toxicological assay can be extrapolated and applied to in vivo studies based on pharmacokinetic modeling. Alfa Chemistry provides professional in vitro toxicological evaluation services of generic drug to identify early generic drug toxicity and to further analyze the structure-toxicity relationship of generic drugs.
Figure 1. An overview of in vitro systems used for toxicity assessment and replacement of animal models. (Srivastava S, et al. 2018)
Common Cell Types Used for In Vitro Cytotoxicity Evaluation
- Limited cell lines derived from normal tissues: IMR-90, MRC-9, WI-38, MRC-5
- Continuous cell lines derived from normal tissues: MDCK, L929, 3T3-L1, COS, Vero, H9c2
- Contiguous cell lines derived from tumor tissue: A549, Caco-2, Hela, HepG2, HL-60, MCF-7
Our Services
We provide a variety of efficient in vitro toxicity screening methods to assess the toxicity propensity and conformational relationship of generic drugs to assist our clients in generic drug selection and optimization. We ensure rapid and timely reporting of the results of multiple analytical methods and dose-dependent relationships, so that our clients can be informed of the potential toxicity of generic drugs as early as possible.
| Service Items | Detection Methods |
| Cytotoxicity | - ATP content assay
- LDH test
- MTT assay
- Cell membrane integrity assay
|
| Mitochondrial Toxicity | - Fluorometric oxygen consumption test
- Mitochondrial membrane potential test
|
| Lysosomal Toxicity | - Neutral red test
- Fluorescence imaging assay
|
| Ion Channel Activity | - Flux assay for functional ions
|
| Genotoxicity | - Bacterial revert mutation test
- Micronucleus test
|
| Cardiotoxicity | - hERG membrane clamp test
- hERG binding assay
|
| Hepatotoxicity | - Hepatocyte activity test
- Steatosis / phospholipid deposition test
|
| Enzyme Induction Assay | |
| Drug Interactions | - Human CYP1A induced cell assay
- P-gp suppressor cell assay
|
| Genotoxicity | |
Advantages of In Vitro Toxicological Evaluation
- Short turnaround time (typically within one week), which improves the efficiency of generic toxicology testing
- Low cost, easy to quantify, and reproducible
- Mechanism of action can be easily identified
- Reduced use of animals
- Most assays are based on high-throughput screening systems
- Low compound dosage
Our in vitro toxicological evaluation services of generic drugs range from the selection of cell types to the identification of evaluation parameters and the selection of suitable assays. Depending on the client's needs, we select the right type of cells, different assays, and different evaluation criteria. Please contact us for more information.
Reference
- Srivastava S, Mishra S, Dewangan J, et al. Principles for in vitro toxicology[M]//In Vitro Toxicology. Academic Press, 2018: 21-43.
