Development of an on-line analytical method for the quantification of carbamate pesticides and metabolites in human matrices

摘要

Worldwide, serious concern has arisen about the increased incidence of learning and developmental disorders in children. From a scientific point of view, there is no doubt that exposure to neurotoxic chemicals during early brain development can adversely affect learning and development. Various recent epidemiological studies have indicated that exposure to low doses of environmental biologically active contaminants during human development can have deleterious effects on cognitive development in childhood. The European commission-funded project DENAMIC "Developmental Neurotoxicity Assessment of Mixtures in Children" investigates neurotoxic effects (e.g. learning and developmental disorders) of low-concentration mixtures of pesticides and a number of common environmental pollutants in children. Because of recent concerns of cognitive and neurobehavioral effects related to pesticide exposure and if proven necessary the possibility to protect future generations by regulatory measures, DENAMIC will primarily focus on possible neurotoxic effects of pesticides (e.g. organophosphate, carbamates, pyrethroids, organochlorine). One of the aims is to study perinatal and early-childhood exposure in maternal urine and cord blood, as well as breast milk and urine of the child. Data and samples from existing European cohorts with different exposure profiles, both pre-and postnatal, (Norway, Netherlands, Slovakia and Spain) are studied, which offers the possibility to distinguish between pre-and postnatal exposure effects and identify the susceptible period. Associations between chemical exposure and learning (cognitive) and neurobehavioural (ADHD, ASD, anxiety) development or disorders will be studied. The aim of this paper is to present the development of an on-line LC-MS/MS for the detection and quantification of carbamates and metabolites in urine, serum and breast milk. The developed sample prepartion method consist of a deconjugation step, and an on-line extraction, clean-up, and separation method combined with LC-MS/MS. The compounds of interested were fractionated using a Restricted Access Material (RAM) from the matrix, and then transferred to the analytical column before detection with LC-MS/MS. Different parameters for the RAM material were optimised to provide acceptable recoveries.