Applications and Toxicity of Tetramethylammonium hydroxide pentahydrate

Tetramethylammonium hydroxide pentahydrate (TMAH) is an ion pairing agent that is commonly used in analytical chemistry. TMAH is utilized in gas chromatography/mass spectrometry (GC/MS), capillary isotachophoresis and capillary zone electrophoresis, and liquid chromatography. TMAOH has been used in the analysis of marine compounds by TLC-pyrolysis-GC/MS and thermal desorption/capillary GC/inductively coupled plasma mass spectrometry.2,3 The use of TMAOH in a capillary zone electrophoresis technique for the separation of inorganic anions has been described.4 A study has been reported on oligonucleotide reassociation in the presence of TMAH. The use of Tetramethylammonium hydroxide pentahydrate in the synthesis of organic and inorganic compounds, such as vinyl halides and tetramethylammonium dithiocarboxylates, has been described.6,7 TMAOH has been utilized in the preparation of iron oxide nanoparticles for application as magnetic resonance imaging contrast agents.

Applications of tetramethylammonium hydroxide pentahydrate

The vast majority of analytical procedures for sample treatment, aimed at elemental determination, are based on decomposition using concentrated acids at high temperatures and/or pressures. Among the sample preparation techniques using alkaline media, those that use strong bases, such as NaOH, LiOH and KOH, water-soluble tertiary amines and tetramethylammonium hydroxide (TMAH) stand out. Tetramethylammonium hydroxide pentahydrate (TMAH) is an alkaline reagent that has been used in the preparation of samples rich in proteins and lipids due to its chemical properties and also for its low consumption and commercial availability, which offers economy, practicality and convenience of use. Treatment methods involving the use of Tetramethylammonium hydroxide pentahydrate can be classified as: (i) procedures based on incubation at room temperature, (ii) procedures based on the use of conventional heating, (iii) procedures based on the use of energy from ultrasound and (iv) procedures based on the use of microwave energy.[1]

With the analysis of the studies available in the literature about Tetramethylammonium hydroxide pentahydrate use in sample preparation, it can be concluded that: (i) In general, it is observed that solubilization using TMAH enable a complete or partial sample dissolution or decomposition, and allow the obtention of a stable solution or slurry in an aqueous medium. Its solubility in water and alcohol allows the complexation and stabilization of volatile elements. This stability also enables speciation studies; (ii) The application of this method as a comparative method or as an alternative to other conventional sample preparation technique has been frequently carried out; (iii) The volume of reagent required (usually in the µL range) is substantially lower, compared to conventional sample preparation methods; (iv) The procedures do not necessarily need heating and, when necessary, gentle heating is used to avoid loss of volatile analytes; (v) In some studies, magnetic stirring or ultrasonic waves are used, with the purpose of reducing the time required for alkaline treatment; (vi) The use of small volumes of high purity Tetramethylammonium hydroxide pentahydrate provides low blanks with better detection limits. Although sample preparation with this reagent presents some advantages, it is not considered a universal reagent, since it is not efficient in solubilizing all types of samples, restricting its efficiency mainly for biological and protein samples. Another disadvantage is the fact that, depending on the type of sample, Tetramethylammonium hydroxide pentahydrate treatment suffers from matrix effect very frequently and, requires the use of the calibration technique by standard addition or matrix matching so that the determination can be carried out with greater reliability.

Tetramethylammonium hydroxide pentahydrate solutions of various concentrations

Tetramethylammonium hydroxide pentahydrate (TMAH, CAS No. 75-59-2) is a strong basic compound that finds application in both scientific and industrial areas. For example, it is used as a reagent in the thermochemolysis of various biopolymers like lignin and cutan or of biomolecules like carbohydrates. Another example is the anisotropic etching of silicon, which is a key technique in the production of micromechanical devices and therefore is widely used especially in the wet processing industry. Due to its acute toxicity in case of contamination implementation of automated concentration monitoring is an important task in the development of new wet processing plants. The measuring unit uses the density of the TMAH solution to check the concentration and therefore needs to be programmed and calibrated with the corresponding information for density/temperature/concentration dependency. Densities for various Tetramethylammonium hydroxide pentahydrate solutions at different temperatures have been determined based on Archimedes’ principle using a hydrostatic balance and a vitreous body with a defined volume. Due to the toxicity of the compound, these data are important especially in the field of wet processing techniques for the automated dosage of Tetramethylammonium hydroxide pentahydrate.[2]

Tetramethylammonium hydroxide pentahydrate poisoning

Tetramethylammonium hydroxide pentahydrate is widely used as a developer or etchant in semiconductor and photoelectric industries. In addition to alkalinity-related chemical burn, dermal exposure to TMAH may also result in respiratory failure and/or sudden death. The latter toxic effect has been of great concern in Taiwan after the occurrence of three fatalities in recent years. To better understand the toxicity following dermal exposure to TMAH, we analyzed all cases with TMAH exposure reported to the Taiwan Poison Control Center (PCC-Taiwan). Case reports. In total, there were 13 cases of such exposure, including three patients who died after being exposed to 25% Tetramethylammonium hydroxide pentahydrate. A worker also developed severe effects manifesting muscle weakness, dyspnea, hyperglycemia, and chemical burn (28% of total body surface area) shortly after an accidental exposure to 2.38% TMAH. He received endotracheal intubation with assisted ventilation for 2 days and survived. Conclusion. Skin corrosive injury related to the alkalinity of TMAH and the ganglionic toxicity of tetramethylammonium ion might contribute to the clinical manifestations that occurred after dermal TMAH exposure. Thorough skin decontamination followed by prompt respiratory support should be the mainstay in the management of dermal Tetramethylammonium hydroxide pentahydrate exposure. Preventive strategies are warranted as well to decrease future occupational TMAH exposures.[3]

References

[1]Cerqueira, U. M. F. M., Alves, J. P. S., Santos, W. N. L., Pita, B. da S., Novaes, C. G., Araújo, S. A., & Bezerra, M. A. (2024). Recent applications of tetramethylammonium hydroxide (TMAH) in the sample preparation for elemental analysis by spectroanalytical techniques. Advances in Sample Preparation, 9, 100104.

[2]Diebold J, Weiß Y, Zürcher S, Schmidt MS. Dataset for density/temperature correlation of tetramethylammonium hydroxide solutions of various concentrations. Data Brief. 2022 Oct 20;45:108679. doi: 10.1016/j.dib.2022.108679. PMID: 36426075; PMCID: PMC9679715.

[3]Lin, Chun-Chi et al. “Tetramethylammonium hydroxide poisoning.” Clinical toxicology (Philadelphia, Pa.) vol. 48,3 (2010): 213-7. doi:10.3109/15563651003627777

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