© Benaki Phytopathological Institute
        
        
          Neonicotinoids Biomonitoring: A review
        
        
          35
        
        
          ments such as air (Dockery and Pope, 1994;
        
        
          Chen and Liao, 2006). Amongst the organ-
        
        
          ic pollutants that impact the environment,
        
        
          pesticides possess a predominant role. In-
        
        
          creasing number of works and modern ap-
        
        
          plications are published in the domain of
        
        
          presence of pesticides in human biological
        
        
          fluids [see (Hernandez
        
        
          et al
        
        
          ., 2005; Inoue
        
        
          et
        
        
          al
        
        
          ., 2007; Jia
        
        
          et al
        
        
          ., 2008)]. The latter are often
        
        
          encompassed in prospective cohort studies
        
        
          that try to elucidate diseases’ causes and as-
        
        
          sociate them with chemicals’ exposure. Such
        
        
          studies have proved their efficacy to un-
        
        
          veil important aspects of prenatal exposure
        
        
          (Bouchard
        
        
          et al
        
        
          ., 2011; Engel
        
        
          et al
        
        
          ., 2007).
        
        
          Human biomonitoring is a leading field
        
        
          in bioanalysis, which covers all parts of the
        
        
          analysis of contaminants in biological flu-
        
        
          ids such as urine, blood, serum, saliva and
        
        
          body tissues. Amongst all matrices (invasive
        
        
          and non-invasive), blood and urine are the
        
        
          most frequently investigated. The collection
        
        
          of biomonitoring data regarding pesticides
        
        
          is of great interest since human exposure is
        
        
          portrayed, and association of concentration
        
        
          levels with potential toxicological effects is
        
        
          plausible.
        
        
          Gagliardi and Pettigrove (2013) report-
        
        
          ed the improvement of aquatic ecosystem
        
        
          health after removal of intensive agriculture
        
        
          from an Australian region. Similarly, minimi-
        
        
          zation of pesticides’ use should be sought
        
        
          projecting in lowered residue levels found
        
        
          in human biological fluids and tissues and
        
        
          subsequently less impact on human health.
        
        
          Given this aspect, NNDs should be encom-
        
        
          passed in monitoring schemes, and collec-
        
        
          tion of pertinent works is of primary impor-
        
        
          tance.
        
        
          The present review summarizes all de-
        
        
          velopments in the field of determination of
        
        
          NNDs and metabolites in human biological
        
        
          fluids. To our knowledge, all available works
        
        
          are included, and highlights of each one are
        
        
          discussed. In addition, case reports are pre-
        
        
          sented that in some cases contain analyti-
        
        
          cal approaches. In the same context, future
        
        
          prospects are provided with emphasis on
        
        
          the directions towards pertinent research
        
        
          endeavors should be focused.
        
        
          
            Bioanalytical Methods
          
        
        
          A biomonitoring study comprises a
        
        
          study population, data and biospecimen
        
        
          collection, sample preparation and purifi-
        
        
          cation, and finally chemical analysis. A fun-
        
        
          damental prerequisite for a human biomon-
        
        
          itoring study is to obtain information from
        
        
          the target population group regarding pos-
        
        
          sible exposure to particular pollutants. By
        
        
          this way, the analytical methods become
        
        
          focused, and results more easily interpret-
        
        
          ed and related to possible health prob-
        
        
          lems that might emerge. However, biologi-
        
        
          cal fluids are complex materials that contain
        
        
          macromolecules such as proteins, and oth-
        
        
          er organic compounds that share common
        
        
          physicochemical parameters with the an-
        
        
          alytes of interest. Thus, the sample prepa-
        
        
          ration step is also critical in providing pure
        
        
          samples, enriched in analytes consider-
        
        
          ing that compounds of interest are usual-
        
        
          ly found at low concentrations. Exceptions
        
        
          are the intoxication incidents in which lev-
        
        
          els are usually higher. One of the most com-
        
        
          mon sample preparation techniques is liq-
        
        
          uid-liquid extraction (LLE) (Kataoka, 2003).
        
        
          It works through the extraction of analytes
        
        
          from the matrix using an organic solvent. Its
        
        
          traditional form has certain downsides that
        
        
          are observed in some occasions, such as the
        
        
          non-miscibility of solvents with the sam-
        
        
          ples, and their difficulty in extracting polar
        
        
          and ionic compounds from aqueous media.
        
        
          Advances on LLE and several of its modified
        
        
          protocols have gained ground the last two
        
        
          decades and are extensively used in analy-
        
        
          sis of contaminants in various commodities
        
        
          (Bosch-Ojeda and Sanchez-Rojas, 2009; de
        
        
          Pinho
        
        
          et al
        
        
          ., 2010). Another routine approach
        
        
          in the sample preparation is solid phase ex-
        
        
          traction (SPE). SPE has been broadly used in
        
        
          preparing the analysis of pesticides in bio-
        
        
          logical fluids (Kataoka, 2003). It possesses
        
        
          certain advantages, such as high recovery,
        
        
          enrichment of analytes through pre-con-
        
        
          centration, relatively short preparation time,
        
        
          and automation compatibility (Li, 2013; Li
        
        
          et
        
        
          al
        
        
          ., 2013; Togola
        
        
          et al
        
        
          ., 2014). Last but not
        
        
          least, protein precipitation is of the oldest
        
        
          ways of processing samples in bioanalysis. It