The technical breakthrough of trifluoromethanesulfonic acid main content determination promotes the high-quality development of the industry

——New detection method helps the precise quality control of pharmaceutical and chemical industry

May 23, 2025. With the widespread application of trifluoromethanesulfonic acid in pharmaceutical synthesis, chemical catalysis, new energy materials and other fields, the importance of its purity detection technology has become increasingly prominent. Recently, the development and application of a number of innovative detection methods have provided a more accurate and environmentally friendly solution for the determination of the main content of trifluoromethanesulfonic acid, pushing the industry towards standardization and efficiency.

Technological innovation: the emergence of highly sensitive detection methods

Suppressed conductivity-ion chromatography 

For impurities such as fluoride ions, chloride ions and sulfates remaining in the production process of trifluoromethanesulfonic acid, researchers used high-capacity IonPac AS18 anion exchange columns and potassium hydroxide gradient elution technology to successfully separate and detect trace impurities in high-concentration, high-acidity matrices. This method has high repeatability (RSD < 3%) and a detection limit as low as 0.1 mg/L (fluoride ions), which is significantly better than traditional ion pair chromatography.

HPLC 

MS technology can accurately determine the residual solvent of trifluoromethanesulfonic acid through C18 chromatographic column and gradient elution program, combined with the high sensitivity of mass spectrometry. For example, the detection limit of genotoxic impurity ethyl trifluoromethanesulfonate in larotaxel raw materials is as low as 1.81 ppb, and the recovery rate is stable at 95.4%~111.4%, providing guarantee for drug safety.

Gas chromatography-mass spectrometry (GC-MS) is used 

To detect genotoxic impurities of trifluoromethanesulfonate esters. The headspace derivatization-GC-MS technology generates stable products through the reaction of the derivatizing agent with the target substance. Combined with the selective monitoring mode of mass spectrometry, trace detection (quantification limit 6.15 ppb) is achieved, filling the technical gap in this field.
in our products is determined by titration, as follows:

1. Instruments, Equipment and Reagents

50mL basic burette, 1mL microburette, NaOH standard solution, phenolphthalein indicator.

2. Analysis steps

① Use a measuring cylinder to measure 30 ml of high-purity water and add it to a 250 mL glass conical flask. Wipe the stoppered conical flask clean and weigh it, which is recorded as m0.

② Take 1.5mL of trifluoromethanesulfonic acid sample and add it to the conical flask, cover it tightly, shake it well, wait for the bottle temperature to drop to room temperature, and when the mist disappears, weigh it again, record it as m1, and shake it well.

③ Add 2-3 drops of phenolphthalein indicator and titrate with 0.5mol/LNaOH standard solution until the solution changes from colorless to pink, and there is no color change within 30 seconds. This is recorded as the endpoint, and the volume of NaOH standard solution consumed is recorded as V. At the same time, perform a blank experiment (titrate with a 1mL microburette) and record the volume of NaOH standard solution consumed, recorded as V0.

3. Calculation:

Where:

X-trifluoromethanesulfonic acid main component content, %; C---

Concentration of NaOH standard solution, mol/L;

V is the volume of NaOH standard solution consumed by the sample, mL;

V0-the volume of the blank NaOH standard solution consumed, mL;

M0 - the mass of the volumetric flask before adding the sample, g;

M1: the mass of the volumetric flask after adding the sample, g.

Industry application: the leap from laboratory to industrialization

Pharmaceutical field : Trifluoromethanesulfonic acid is a strong acid catalyst, and its purity directly affects the efficiency of drug synthesis. For example, the GC-MS method is used to accurately control the genotoxic impurities in the raw materials of larotaxel to ensure the safety of the drug.

Chemical manufacturing : By optimizing the preparation process, we produce 1-ethyl-3-methylimidazolium trifluoromethanesulfonate with a purity of more than 99.5%. Its testing process covers pH determination, heavy metal analysis and spectrophotometry, which helps to promote the high-end development of ionic liquid materials.

Food safety : The trifluoromethanesulfonic acid hydrolysis-HPLC method developed by the Jiangsu Academy of Agricultural Sciences can efficiently detect bound deoxynivalenol (DON) in wheat. The hydrolysis conditions are mild (60°C, 1.0 mol/L acid concentration), providing a new means for monitoring food toxins.

Standardization process: Standardization of testing methods

My country has gradually established a trifluoromethanesulfonic acid testing standard system, covering a variety of technologies such as weight method, ultraviolet absorption method, and spectroscopy. For example:

GB/T 6048-2006 specifies the quality analysis process of trifluoromethanesulfonic acid;

ISO/IEC 7597:2016 sets clear requirements for rapid dissolution testing.

In addition, third-party testing agencies certified by CMA and CNAS provide authoritative reports to promote mutual recognition of industry test results.

Future Outlook: Green and Intelligent Go Hand in Hand

With the upgrading of environmental protection requirements, the methanesulfonic acid (MSA) system has gradually replaced the traditional phenolsulfonic acid system due to its low pollution characteristics. China's independently developed MSA high-speed tin plating technology optimizes the stability of the plating solution, reduces tin consumption (1.3% vs. traditional 4.6%), and supports 500 m/min high-speed production, opening up new scenarios for the application of trifluoromethanesulfonic acid in high-end manufacturing.

In the future, intelligent detection systems that combine artificial intelligence and automated instruments are expected to further improve detection efficiency, while miniaturization technologies such as microfluidic chips may promote the popularization of rapid on-site testing.

Conclusion 

The breakthrough in the determination of trifluoromethanesulfonic acid content not only ensures the quality and safety of downstream products, but also promotes the upgrading and transformation of multiple industries such as medicine, chemical industry, and food. With technological innovation and standard improvement, China is moving towards a global leading position in the field of high-end chemical testing.