Liquid chromatography and mass spectrometry determination of aromatic amines in hydrolysed urine from workers exposed to thermal degradation products of polyurethane

Chromatographia - An LC-MS method is described for the determination of 4,4′-MDA (4,4′-methylene dianiline) in hydrolysed urine as a biomarker for exposure to 4,4′-MDI...     

Trace analysis of airborne 1,6-hexamethylenediisocyanate and the related aminoisocyanate and diamine by glass capillary gas chromatography

A capillary gas chromatographic method was developed for the analysis of complex air mixtures of 1,6-hexamethylenediisocyanate, 1,6-hexamethyleneaminoisocyanate and 1,6-hexamethylenediamine. The method is based on derivatization in the sampling step of the reactive isocyanate groups to corresponding urethane groups by the alkaline ethanolic solvent and a subsequent derivatization of remaining amino groups to amide groups with heptafluorobutyric acid anhydride. The overall procedure, including sampling, gave a linear response at air concentrations of 3-300 micrograms/m3 for 1,6-hexamethylenediisocyanate with a precision of ca. 4% at 15 micrograms/m3 and a detection limit of ca. 0.2 microgram/m3 using nitrogen selective detection. In a field measurement of air concentrations in welding work on lacquered metal parts at a motor-car workshop, concentrations of 1,6-hexamethylenediisocyanate above 600 micrograms/m3 were found. Also 1,6-hexamethyleneaminoisocyanate and 1,6-hexamethylenediamine were found at concentrations of the order of 15% of the 1,6-hexamethylenediisocyanate concentration.     

Determination of airborne isocyanates as di-n-butylamine derivatives using liquid chromatography and tandem mass spectrometry

A method for the determination of isocyanates as di-n-butyl amine (DBA) derivatives using tandem mass spectrometry (MS/MS) and electrospray ionisation (ESI) is presented. Multiple-reaction monitoring (MRM) of the protonated molecular ions and corresponding deuterium-labelled d₉-DBA derivatives resulted in selective quantifications with correlation coefficients >0.998 for the DBA derivatives of isocyanic acid (ICA), methyl isocyanate (MIC), ethyl isocyanate (EIC), propyl isocyanate (PIC), phenyl isocyanate (PhI), 1,6-hexamethylene diisocyanate (HDI), 2,4-, 2,6-toluene diisocyanate (TDI), isophorone diisocyanate (IPDI), 4,4′-methylenediphenyl diisocyanate (MDI), 3-ring MDI, 4-ring MDI, HDI-isocyanurate, HDI-diisocyanurate, HDI-biuret and HDI-dibiuret. The instrumental precision for 10 repeated injections of a solution containing 0.1 μg ml⁻¹ of the studied derivatives was <2%. Performing MRM of the product ion [DBA + H]⁺ (m/z = 130) from the protonated molecular ion resulted in the lowest detection limits, down to 10 amol (for TDI). Quantification of concentrations below 10⁻⁶ of the occupational exposure limit (OEL) for TDI during 10 min of air sampling was made possible. In an effort to control the formation of alkali adducts, addition of lithium acetate to the mobile phase and monitoring of lithium adducts was evaluated. Having lithium present in the mobile phase resulted in complete domination of [M + Li]⁺ adducts, but detection limits for the studied compounds were not improved. Different deuterium-labelled derivatives as internal standards were evaluated. (1) DBA derivatives of deuterium-labelled isocyanates (d₄-HDI, d₃-2,4-TDI, d₃-2,6-TDI and d₂-MDI), (2) d₉-DBA derivatives of the corresponding isocyanates and (3) d₁₈-DBA derivatives of the corresponding isocyanates. An increase in number of deuterium in the molecule of the internal standard resulted in an increase in instrumental precision and a decrease in correlation within calibration series.     

Determination of piperazine in working atmosphere and in human urine using derivatization and capillary gas chromatography with nitrogen- and mass-selective detection

A reliable routine method is presented for the determination of piperazine down to the sub-ppm level in aqueous solutions and in urine. The method includes a two-phase derivatization procedure with ethyl- or isobutyl chloroformate as the reagent, followed by a capillary gas chromatographic determination using nitrogen- or mass selective detection. The addition of ammonia ensured a quantitative recovery. Detection limits for piperazine in urine were ca. 20 ng/ml using nitrogen-selective and ca. 1 ng/ml with mass-selective detection. The calibration plots were linear in the investigated range, 100-10,000 ng/ml with nitrogen-selective and 30-3000 ng/ml with mass-selective detection. The precision was ca. 6% at a concentration of 300 ng/ml. Acid anhydrides were investigated as alternative reagents in the two-phase derivatization procedure, and heptafluorobutyric acid anhydride in aqueous solutions gave approximately 100% recovery. However, in urine the recoveries of the investigated acid anhydride derivatives were unsatisfactory.     

Determination of hexahydrophthalic anhydride in air using gas chromatography.

Two methods for the determination of hexahydrophthalic anhydride (HHPA) in air were developed. In a solid sorbent method, HHPA was sampled in Amberlite XAD-2 tubes, eluted in toluene and analysed by gas chromatography with flame ionization detection. The sampling rates were 0.2 and 1.0 l/min. At 15 micrograms/m3 (relative humidity less than 2%) and 27 micrograms/m3 (relative humidity 70%) no breakthrough was observed. However, at 160 micrograms/m3 (relative humidity less than 2%), 6% breakthrough was found. The sampling efficiency of the sampling rates 0.2 and 1.0 l/min did not differ. In a bubbler method, HHPA was sampled in bubblers filled with 0.1 M sodium hydroxide solution. The sodium salt of hexahydrophthalic acid was formed. No breakthrough was observed using a sampling rate of 1.0 l/min. The samples were stable during storage for eight weeks in a refrigerator. The HHP acid was esterified with methanol-boron trifluoride and analysed by gas chromatography-flame ionization detection. Apparatus for the generation of standard atmospheres of HHPA, in the range of 10-3000 micrograms/m3, was developed using the diffusion principle. For the solid sorbent method the precision (coefficient of variation) of the overall method was 2-7%, and for the bubbler method 3-19% (range 15-160 micrograms HHPA/m3; relative humidity = less than 2-70%). A comparison between the two methods was performed using the standard atmosphere. The concentrations found by the solid sorbent method were 86-98% of those found by the bubbler method (range 15-160 micrograms HHPA per m3; relative humidity = less than 2-70%). In work environment air, 93% was found using the solid sorbent method relative to the bubbler method at a mean concentration of 330 micrograms/m3 (coefficient of variation = 39%; range 200-540 micrograms/m3). For both methods, concentrations greater than 3 micrograms/m3 could be quantified at 60 min sampling with a sampling rate of 1.0 l/min.     

Thermospray mass spectrometry of aliphatic diamines derivatized with trifluoroethyl chloroformate,with special reference to the biological monitoring of hexamethylenediisocyanate (HDI) and isophoronediisocyanate (IPDI)

Chromatographia - 1,6-Diaminohexane (DAH, 1,6-hexamethylene diamine) and isophorone diamine (IPDA) have been derivatized with trifluoroethyl chloroformate (TFECF) using a two-phase procedure....     

Chromatographic determination of amines in biological fluids with special reference to the biological monitoring of isocyanates and amines. IV. Determination of 1,6-hexamethylenediamine in human urine using capillary gas chromatography and selective ion monitoring

A capillary gas chromatographic (GC) method was developed for the determination of 1,6-hexamethylenediamine (HDA) in hydrolysed human urine. The method was based on a derivatization procedure with heptafluorobutyric anhydride. The amides formed were determined using capillary GC with selected ion monitoring in the chemical ionization mode with ammonia as reagent gas. The overall recovery was 34% for a concentration of 100 micrograms/l of HDA in urine. The minimum detectable concentration in urine was below 0.5 microgram/l. The precision of the method was 5% (n = 9). Deuterium-labelled HDA [H2NC2H2(CH2)4C2H2NH2] was used as the internal standard. A male subject was exposed to hexamethylene diisocyanate (HDI) for 7.5 h in a test chamber. The average air concentration of HDI was ca. 30 micrograms/m3, which corresponds to ca. 85% of the threshold limit value in Sweden (35 micrograms/m3). The half time of urinary levels of HDA was ca. 1.4 h and more than 90% of the urinary elimination was completed within 4 h after the exposure. The amount of HDA excreted in urine was ca. 10 micrograms, corresponding to ca. 10% of the estimated inhaled dose of HDI.     

The solubility of tri-n-octylamine in water and phosphoric acid solutions

The solubility of tri-n-octylamine (TOA) in water and phosphoric acid is reported. Equilibration is achieved by circulating the solutioin through PVC pieces saturated with the absorbed amine in a glass tube. The dissolved TOA is determined by capillary gas chromatography which can detect amine concentrations down to 10 μg l^?1. The solubility of TOA in water is 0.039 mg l^?1 and in 5.5 M phosphoric acid 0.82 mg l^?1; these values are much lower than those reported in the literature.     

Trace analysis of airborne aromatic isocyanates and related aminoisocyanates and diamines using high-performance liquid chromatography with ultraviolet and electrochemical detection

A high-performance liquid chromatographic method was developed for trace analysis of complex air mixtures containing 2,6- and 2,4-toluenediisocyanates and related aminoisocyanates and diamines. The accuracy was tested at isocyanate concentrations of 2-1000 microg/m3 in air. The method is based on derivatization in the sampling step of isocyanate functions to corresponding urethane groups, with alkaline ethanol as the sampling and reacting medium. The derivatives formed, toluenediurethanes and tolueneaminourethanes, and unreacted diamines were detected by UV or electrochemically, the electrochemical detection being one order of magnitude more sensitive. Using an enrichment column, detection limits of ca. 0.05 pg/microl were obtained with electrochemical detection at a potential of 950 mV, which corresponds to air concentrations of 0.1 microg/m3 with 5 min sampling time at a rate of 11/min. The precision in the measurements were ca. 4% at concentrations of 6 microg/m3. A field measurement was performed concerning flame lamination of toluenediisocyanate-based polyurethane and cloth. Isocyanates, aminoisocyanates and diamines were found at air concentrations of 1-100 microg/m3.     

Evaluation of Chromatographic Methods for the Determination of Isocyanates in Air

Abstract

Chromatographic methods for the determination of toluene diisocyanates (TDI) in air, at concentrations of 20–40μg/m³, were evaluated. Test atmospheres were generated by a gas-phase permeation principle. The GC method was based on sampling in impingers containing an acidic aqueous solution (0.4 M HC1), where the isocyanates are hydrolysed into the corresponding amines. The pentafiuoropropionic acid derivatives of the amines were analysed using glass capillary GC with thermionic detection. The HPLC methods were based on reaction with the amine reagents 9-(N-methylaminomethyl)-anthracene (1 × 10^?4M in toluene) and 1-(2-methoxyphenyl)-piperazine (2 × 10^?4M in toluene). The urea derivatives were determined using UV detection. The sampling efficiency for gaseous TDI with toluene as absorbing solution was 97%. Sampling efficiencies in various acidic aqueous solutions were 83–88%. The relative standard deviation for the various methods was ca. 6%. No sampling losses for TDI, due to influences of interfering substances (diethylamine, dimethylethylamine, N-methylmorpholine, DABCO, aniline, ethanol, phenol) using acidic aqueous 0.4 M HC1 were obtained. Diethylamine, N-methylmorpholine and DABCO affected the analytical results when toluene solutions of the amine reagents MAMA and MPP were used.