Determination of carbofuran, carbaryl and their main metabolites in plasma samples of agricultural populations using gas chromatography-tandem mass spectrometry

• Published in: Analytical and bioanalytical chemistry 2006-08, Vol.385 (8), p.1444-1456
• Main Authors: Petropoulou, Syrago-Styliani E, Tsarbopoulos, Anthony, Siskos, Panayotis A
• Format: Article
• Language: English
• Subjects: Acidic oxides; Agriculture; Ascorbic acid; Biological monitoring; Biomarkers of exposure; Biomonitoring; Blood plasma; Carbaryl; Carbaryl - blood; Carbaryl - metabolism; Carbofuran; Carbofuran - blood; Carbofuran - metabolism; Chromatography; Denaturation; Gas chromatography; Gas Chromatography-Mass Spectrometry - methods; Human plasma samples; Humans; Hydrophobicity; Ketones; Lipophilic; Mass spectrometry; Mass spectroscopy; Mathematical analysis; Metabolites; N-methylcarbamates; Naphthalene; Naphthol; Optimization; Pesticides; Phenols; Plasma; Plasma proteins; Reproducibility of Results; Scientific imaging; Solid phases; Spectroscopy; Tandem mass spectrometry; Tandem Mass Spectrometry - methods; Trifluoroacetic acid; Trifluoroacetyl; Volatile compounds
• ISSN: 1618-2642; 1618-2650
• DOI: 10.1007/s00216-006-0569-0

A gas chromatography-tandem mass spectrometric (GC-MS/MS) method has been developed for the determination of carbofuran (2,3-dihydro-2,2-dimethylbenzofuran-7-yl methylcarbamate), carbaryl (1-naphthyl-N-methylcarbamate) and their main metabolites in human blood plasma. Optimization of the isolation of the compounds from plasma matrix included the precipitation, denaturation and digestion of plasma proteins. Derivatization was achieved by the use of trifluoroacetic acid anhydride and was optimized for temperature, time and volume of derivatization agent. In the proposed method, a mild precipitation technique was applied using β-mercaptoethanol and ascorbic acid in combination with solid-phase extraction technique using Oasis HLB (Hydrophobic Lipophilic Balance) cartridges for further clean up of samples. Carbamate linkage was not hydrolyzed to its phenol product, but both carbamate phenol and ketones were transformed into trifluoroacetyl derivatives in order to become volatile compounds and were determined using tandem mass spectrometry. The linearity of the method was shown for nine concentrations in the range of 0.50-250 ng mL-¹ in fortified plasma aliquots. Limits of detection (LODs) for all compounds ranged from 0.015-0.151 ng mL-¹. Inter-day and intra-day assays (RSD) for all compounds, at three concentration levels of 2.5, 25 and 100 ng mL-¹ (n=3) in fortified plasma samples were less than 18%. Accuracy (%E r) was calculated at three concentration levels, 8, 80 and 160 ng mL-¹ (n=3), and ranged from -12.0 to 15.0%. Matrix effect was evaluated so mean recoveries were calculated for all compounds and ranged from 81-107%. Specificity for the use of this method to biological monitoring studies was achieved including four main metabolites of CF, 1-naphthol and 2-naphthol from the naphthalene metabolism pathways, and both the parent compound of carbofuran and carbaryl. The proposed method was applied to plasma samples of pesticide users.