Gas-chromatography mass-spectrometry determination of phthalic acid in human urine as a biomarker of folpet exposure

Abstract

Agricultural workers are exposed to folpet, but biomonitoring data are limited. Phthalimide (PI), phthalamic acid (PAA), and phthalic acid (PA) are the ring metabolites of this fungicide according to animal studies, but they have not yet been measured in human urine as metabolites of folpet, only PA as a metabolite of phthalates. The objective of this study was thus to develop a reliable gas chromatography-tandem mass spectrometry (GC-MS) method to quantify the sum of PI, PAA, and PA ring-metabolites of folpet in human urine. Briefly, the method consisted of adding p-methylhippuric acid as an internal standard, performing an acid hydrolysis at 100 °C to convert ring-metabolites into PA, purifying samples by ethyl acetate extraction, and derivatizing with N,O-bis(trimethylsilyl)trifluoro acetamide prior to GC-MS analysis. The method had a detection limit of 60.2 nmol/L (10 ng/mL); it was found to be accurate (mean recovery, 97%), precise (inter- and intra-day percentage relative standard deviations <13%), and with a good linearity (R (2) > 0.98). Validation was conducted using unexposed peoples urine spiked at concentrations ranging from 4.0 to 16.1 μmol/L, along with urine samples of volunteers dosed with folpet, and of exposed workers. The method proved to be (1) suitable and accurate to determine the kinetic profile of PA equivalents in the urine of volunteers orally and dermally administered folpet and (2) relevant for the biomonitoring of exposure in workers.

Toxicokinetics of captan and folpet biomarkers in dermally exposed volunteers

“…A gas chromatography mass spectrometry (GC-MS) method was developed for the analysis of phthalic acid in urine, as previously described (Berthet et al, 2011c). In short, urine samples were subjected to an acid hydrolysis prior to liquidliquid extraction with ethyl acetate and derivatization with N,Obis(trimethylsilyl)trifluoroacetamide (BSTFA).…”

Application of Dissolvable Layered Double Hydroxides As Sorbent in Dispersive Solid-Phase Extraction and Extraction by Co-Precipitation for the Determination of Aromatic Acid Anions

“…16,17 Mandelic acid (used as skin peel in cosmetics) and phthalic acid can be considered as biomarkers of occupational exposure to toxic compounds. 18,19 These compounds may be detected in human urine 16−21 or other aqueous samples. 22−24 The main purpose of this work is to develop an interesting new approach to sorbent-based extraction.…”

Toxicokinetics of captan and folpet biomarkers in orally exposed volunteers

“…A gas chromatography mass spectrometry (GC‐MS) method was developed for the analysis of phthalic acid in urine, as previously described (Berthet et al , ). In short, urine samples were subjected to an acid hydrolysis prior to liquid‐liquid extraction with ethyl acetate and derivatization with N , O ‐bis(trimethylsilyl)trifluoroacetamide (BSTFA).…”