Talking about: Sulfonate Drugs & Sulfonate Gene Toxicity

WenJohnson

In recent years, the review of genetic toxic substances by the drug review department has become stricter and more demanding.

For the "sulfonate drugs" we are going to talk about today, the "sulfonic acids" required for salt formation are themselves potential hazards of genotoxic substances, but they have not affected their great help to the successful marketing of the improved drug properties, and until Today, this method of salt formation is still in use no matter at home or abroad.

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Nefinavir mesylate is an HIV-1 protease inhibitor for the treatment of HIV-1 infection; it was developed by Agouron, approved by the US FDA in 1997, approved by the European EMA in 1998, and approved by the Japanese PMDA in 1998 , Jointly sold by Agouron and ViiV Healthcare in the US market under the trade name Viracept®.

On June 6, 2007, the European EMA discovered that some batches of anti-AIDS drug Viracept, that is, nelfinavir mesylate contains high doses of genotoxic impurity ~ ethyl methanesulfonate, and decided to recall the drug produced by Roche Pharmaceuticals.

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Table 1: Acceptable limits of genotoxic impurities in the clinical phase of drugs

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When the sample cannot meet the conditions of direct injection analysis, the sample needs to be pre-processed.

The GC method is mainly used for the determination of volatile components.

Compared with the GC method, the LC method can analyze the non-volatile components, and the sample load is also larger, the method is simple and feasible.

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Genotoxic impurities mainly come from starting materials, intermediates, reagents and reaction by-products in the synthesis of APIs.
In addition, drugs may also degrade to produce genotoxic impurities during synthesis, storage, or formulation.
As potential genotoxic impurities, acid ester compounds should be avoided as much as possible.
Studies have reported the formation of sulfonate esters and various factors affecting their degradation, including temperature, alcohols, moisture, acids, alkalis, salts, etc.
The results show that in neutral or trace amounts of alkali excess (such as 2,6-dimethyl The formation of these impurities can be avoided under the conditions of base pyridine), anhydrous, low-concentration alcohol, acids weaker than methanesulfonic acid (such as phosphoric acid), and salts (such as sodium perchlorate).
There is currently no report indicating that sulfonate compounds are produced by degradation in other drugs.

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Global "sulfonate drugs"

Through the drug crossing data query, 72 sulfonate drugs have been marketed, 3 NDA varieties, 14 clinical phase III, 17 clinical phase II, and 12 clinical phase I; in terms of treatment, they are mainly distributed in tumors and heart Cerebrovascular, nervous system, infection, respiratory system, endocrine, etc.
; for some drugs, see the table below for details (readers can inquire about it).

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Domestic "sulfonate drugs"

For further inquiries, domestically developed/under-study drugs, "sulfonate drugs", have 1 approved marketed product, 2 NDA products, 5 clinical phase III products, 4 clinical phase II products, and 11 clinical phase I products; partly For drugs, see the table below for details.

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Summary

Be cautious of sulfonate drugs, this is right, after all, there are potential risks! But sometimes, sulfonate drugs do have better data support in pharmacy! Therefore, how to design and control in this process is very necessary!

What I want to say here is that gene toxic substances are really annoying, but we can't stay away from it one-sidedly.
In the process, it is good to be able to avoid nature.
If it cannot be avoided, then we will control + study it! In short, don't give up eating because of choking, and in-depth research in the process, to further feel the importance of technology, there will still be a lot of fun!