Telemisartan is excluded from impurity survey

In case of Telmisartan, impurities are unlikely because there is no tetrazole ring

The MFDS has expanded the scope of the impurity investigation to ARB drugs as a whole.

 

However, Telmisartan·Azilsartan·Eprosartan were excluded from the list of additional investigations.

 

The pharmaceutical industry understands that Telmisartan was excluded from the impurity survey because it does not have a tetrazole ring.

 

The MFDS said on the 23rd, an official letter was sent to analyze and evaluate the possibility of impurities occurring in Olmesartan, Fimasartan, and Candesartan.

 

The company that owns the drug in question shall analyze and submit the possibility of 'AZBT/Azido Methyl Bipheny Tetrazole' by the 22nd of next month.

 

The scope of impurity investigation has been expanded from the existing Irbesartan·Losartan·Valsartan to the entire ARBs.

 

A total of nine ARB-based drugs are licensed in South Korea.

 

Losartan, Valsartan, Azilsartan, Eprosartan, Olmesartan, Fimasartan, Candesartan, Irbesartan and Telmisartan.

 

Telmisartan, Eprosartan and Azilsartan were excluded from further investigations by the MFDS.

 

797 products containing Telmisartan such as Micardis, 5 Azilsartan products such as Edarbi, and 2 items of Eprosartan such as Teveten do not need to be further investigated.

 

◆AZBT and NDMA can occur during the synthesis of tetrazole rings

Tetrazole ring molecular structure.

 

Many ARBs contain this molecular structur

The pharmaceutical industry understands that the shape of each component's molecular structure influenced the MFDS' decision on the scope of the investigation.

 

The MFDS ordered an investigation into impurities, limiting only ingredients with "tetrazole rings" in molecular structure.

 

The MFDS estimated that Azido impurities are produced by reacting 'Br-OTBN (4'-Bromomethyl-2-cyano-biphenyl) and 'Sodium Azide (NaN3).

 

Br-OTBN is the main intermediate in the synthesis of tetrazole rings.

 

Add a reagent called Sodium Azide and the tetrazole ring is synthesized.

 

In other words, the reagent (azide) used to synthesize tetrazole rings may have been produced as a "suspicious substance (AZBT)" in response to certain conditions.

 

It is estimated that NDMA (N-Nitrosodimethylamine), which was detected during the Valsartan crisis in 2018, also occurred after a similar process.

 

At that time, the MFDS (DMF), which was used as a solvent to make the tetrazole ring, was decomposed into dimethylamine during the high temperature process, and was produced by reacting to NaNO2.

 

The same is true of NDEA (Nitrosodiethylamine).

 

It is believed to have been produced by reacting to the impurities dimethylamine and nitrite contained in the triethanolamine (TEA) itself used as reagents.

 

The MFDS judges that ARB drugs, including tetrazole rings, are likely to develop AZBT or NDMA and NDA at any time.

 

◆Of 9 ARB drugs, six contain tetrazole rings Looking at the molecular structure of ARB drugs, tetrazole rings are found only in Eprosartan, Olmesartan,Fimasartan,Candesartan,Irbesartan, Losartan.

 

This is not the case with Telmisartan, Azilsartan, and Eprosartan.

 

The tetrazole ring determines whether the Ministry of Food and Drug Safety will order an investigation into the possibility of impurities.

 

An official from a pharmaceutical company said, "Even if it is the same ingredient, the possibility of detecting impurities is divided depending on which reagent or solvent is used." "In addition, the possibility of occurrence varies depending on whether or not there is a tetrazole ring in the molecular structure.

 

"In Telmisartan's case, there is little chance of impurities occurring because there is no tetrazole ring."