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Validation and application of a headspace-gas chromatography-mass spectrometric method for determination of toluene and 2-butanol in urine

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Toluene, widely used across various industries, poses significant health risks upon prolonged exposure, such as hallucinations and visual impairment. The Chemical Substances Control Act classifies toluene and butane as hallucinogenic substances, necessitating the strict regulation of their inhalation. Conventionally, toluene exposure has been assessed by measuring hippuric acid levels in urine. However, as hippuric acid is an endogenous substance, its reliability as a marker of toluene inhalation is limited. Similarly, 2-butanol metabolizes to 2-butanone, which is also present in the urine of individuals with certain medical conditions, rendering it unsuitable as a definitive marker of butane abuse. This study aimed to develop and validate a quantitative analysis method for detecting toluene and 2-butanol in urine, addressing challenges associated with assessing exposure to these chemicals. We developed a cryotrap-free quantitative analytical method using an HP-1 column (100 m × 0.25 mm i.d. × 0.5 μm). Sample preparation involved the addition of sodium sulfate and an internal standard to the urine samples. The method demonstrated excellent selectivity, with limits of quantitation and detection at 0.001 and 0.0003 µg/mL for toluene, and 0.01 and 0.002 µg/mL for 2-butanol, respectively. The calibration curve exhibited high linearity (r2 > 0.9996) across a quantitative range (0.002 – 0.2 µg/mL for toluene and 0.4 – 6 µg/mL for 2-butanol), ensuring accurate measurement. This method exhibits significant potential for effectively identifying toluene and butane abuse and offers a valuable tool for regulatory agencies and healthcare professionals to protect public health.

Abstract

Toluene, widely used across various industries, poses significant health risks upon prolonged exposure, such as hallucinations and visual impairment. The Chemical Substances Control Act classifies toluene and butane as hallucinogenic substances, necessitating the strict regulation of their inhalation. Conventionally, toluene exposure has been assessed by measuring hippuric acid levels in urine. However, as hippuric acid is an endogenous substance, its reliability as a marker of toluene inhalation is limited. Similarly, 2-butanol metabolizes to 2-butanone, which is also present in the urine of individuals with certain medical conditions, rendering it unsuitable as a definitive marker of butane abuse. This study aimed to develop and validate a quantitative analysis method for detecting toluene and 2-butanol in urine, addressing challenges associated with assessing exposure to these chemicals. We developed a cryotrap-free quantitative analytical method using an HP-1 column (100 m × 0.25 mm i.d. × 0.5 μm). Sample preparation involved the addition of sodium sulfate and an internal standard to the urine samples. The method demonstrated excellent selectivity, with limits of quantitation and detection at 0.001 and 0.0003 µg/mL for toluene, and 0.01 and 0.002 µg/mL for 2-butanol, respectively. The calibration curve exhibited high linearity (r2 > 0.9996) across a quantitative range (0.002 – 0.2 µg/mL for toluene and 0.4 – 6 µg/mL for 2-butanol), ensuring accurate measurement. This method exhibits significant potential for effectively identifying toluene and butane abuse and offers a valuable tool for regulatory agencies and healthcare professionals to protect public health.

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