Quantitative determination of urinary metabolites of geraniol by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). 2020

Thomas Jäger, and Sandra Bäcker, and Thomas Brodbeck, and Edgar Leibold, and Michael Bader
BASF SE, Corporate Health Management, Ludwigshafen, Germany. thomas.b.jaeger@basf.com.

Geraniol is a fragrance which occurs in natural terpene oil or is chemically synthesized on a large scale. It is used in a wide variety of consumer products such as perfumes, deodorants, household products and cosmetics. Hence, not only industry workers in the production of geraniol, but also consumers can come into contact with the substance. Human biomonitoring (HBM), i.e. the analytical determination of substances and their metabolites in human biological material, is a key element in the analysis and assessment of the distribution and intensity of occupational and environmental exposure of humans. Therefore, a procedure for the quantitative determination of the urinary metabolites Hildebrandt acid, geranic acid, 3-hydroxycitronellic acid and 8-carboxygeraniol as potential biomarkers of geraniol exposure was developed and validated. The method is based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) after enzymatic hydrolysis and liquid-liquid extraction (LLE) of the target analytes. The limit of quantification (LOQ) is 1.5 μg L-1 for 8-carboxygeraniol, 2.7 μg L-1 each for Hildebrandt acid and geranic acid, and 1.8 μg L-1 for 3-hydroxycitronellic acid. The method was applied to urine samples of 41 persons without occupational exposure to geraniol. Hildebrandt acid and geranic acid were detected in all samples, 8-carboxygeraniol in 83% and 3-hydroxycitronellic acid in 81% of the samples. Hildebrandt acid (median: 313 μg L-1, range: 37-1966 μg L-1) was the most abundant metabolite, followed by geranic acid (93 μg L-1; 9-477 μg L-1), 3-hydroxycitronellic acid (18 μg L-1; <LOQ to 70 μg L-1) and 8-carboxygeraniol (9 μg L-1; <LOQ to 46 μg L-1). Hildebrandt acid, geranic acid and 3-hydroxycitronellic acid apparently represent larger relative fractions of the eliminated metabolites, but they are not strictly specific for geraniol since they are metabolites of other terpenes as well, such as citral. In contrast, geraniol seems to be the only parent compound for 8-carboxygeraniol, which makes this metabolite a promising candidate for specific human biomonitoring and risk assessment.

UI MeSH Term Description Entries
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D002853 Chromatography, Liquid Chromatographic techniques in which the mobile phase is a liquid. Liquid Chromatography
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000080462 Acyclic Monoterpenes Linear compounds that contain a single monoterpene unit. Monoterpenes, Acyclic
D053719 Tandem Mass Spectrometry A mass spectrometry technique using two (MS/MS) or more mass analyzers. With two in tandem, the precursor ions are mass-selected by a first mass analyzer, and focused into a collision region where they are then fragmented into product ions which are then characterized by a second mass analyzer. A variety of techniques are used to separate the compounds, ionize them, and introduce them to the first mass analyzer. For example, for in GC-MS/MS, GAS CHROMATOGRAPHY-MASS SPECTROMETRY is involved in separating relatively small compounds by GAS CHROMATOGRAPHY prior to injecting them into an ionization chamber for the mass selection. Mass Spectrometry-Mass Spectrometry,Mass Spectrometry Mass Spectrometry,Mass Spectrometry, Tandem
D057230 Limit of Detection Concentration or quantity that is derived from the smallest measure that can be detected with reasonable certainty for a given analytical procedure. Limits of Detection,Detection Limit,Detection Limits

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