Reviewing the Analytical Methodologies to Determine the Occurrence of Citrinin and Its Major Metabolite, Dihydrocitrinone, in Human Biological Fluids

Abstract

Until now, the available data regarding citrinin (CIT) levels in food and the consumption of contaminated foods are insufficient to allow a reliable estimate of intake. Therefore, biomonitoring configuring analysis of parent compound and/or metabolites in biological fluids, such as urine or blood, is being increasingly applied in the assessment of human exposure to CIT and its metabolite, dihydrocitrinone (DH-CIT). Most studies report urinary levels lower for the parent compound when compared with DH-CIT. A high variability either in the mean levels or in the inter-individual ratios of CIT/DH-CIT between the reported studies has been found. Levels of DH-CIT in urine were reported as being comprised between three to seventeen times higher than the parent mycotoxin. In order to comply with this objective, sensitive analytical methodologies for determining biomarkers of exposure are required. Recent development of powerful analytical techniques, namely liquid chromatography coupled to mass spectrometry (LC-MS/MS) and ultra-high-performance liquid chromatography (UHPLC-MS/MS) have facilitated biomonitoring studies, mainly in urine samples. In the present work, evidence on human exposure to CIT through its occurrence and its metabolite, in biological fluids, urine and blood/plasma, in different countries, is reviewed. The analytical methodologies usually employed to evaluate trace quantities of these two molecules, are also presented. In this sense, relevant data on sampling (size and pre-treatment), extraction, cleanup and detection and quantification techniques and respective chromatographic conditions, as well as the analytical performance, are evidenced.

Citrinin Dietary Exposure Assessment Approach through Human Biomonitoring High-Resolution Mass Spectrometry-Based Data

“… 27 In this line, the sum of CIT and DH-CIT in urine has been proposed as an effective biomarker to assess the exposure to CIT. 25 , 26 , 28 , 29 Several biomonitoring surveys have reported the occurrence of CIT and DH-CIT in urines from different human cohorts from Belgium, 30 − 32 Czech Republic, 33 Portugal, 34 , 35 Germany, 36 − 39 Haiti, 39 Bangladesh, 39 − 43 Nigeria, 44 Turkey, 36 and Tunisia. 45 Biomarkers should be measured by sensitive and specific analytical methods able to detect even a low level of exposure.…”

“…A complementary approach to assess mycotoxin exposure is biomonitoring, which involves the analysis of parent compounds and/or their metabolites in human biological samples . In this line, the sum of CIT and DH-CIT in urine has been proposed as an effective biomarker to assess the exposure to CIT. ,,, Several biomonitoring surveys have reported the occurrence of CIT and DH-CIT in urines from different human cohorts from Belgium, − Czech Republic, Portugal, , Germany, − Haiti, Bangladesh, − Nigeria, Turkey, and Tunisia . Biomarkers should be measured by sensitive and specific analytical methods able to detect even a low level of exposure.…”

Citrinin Exposure in Germany: Urine Biomarker Analysis in Children and Adults

“…First reports are those by Blaszkewicz et al [ 15 ] and by Ali et al [ 16 ] on biomarker occurrence in urines from German adults, and a comparative study of the urinary biomarker excretion patterns in Bangladesh, Germany, and Haiti by a multi-mycotoxin method [ 17 ]. More recent results of CIT biomarker analysis in cohorts from several countries, by targeted or by multi-mycotoxin methods, have been reviewed [ 18 , 19 , 20 ]; these data show widespread exposure to this nephrotoxic food contaminant, as well as variations in the occurrence and urine levels of CIT and DH-CIT in different parts of the world.…”

Human Biomonitoring of Selected Hazardous Compounds in Portugal: Part II—Lessons Learned on Mycotoxins

“…CIT is a polyketide mycotoxin produced by fungi belonging to the genera Penicillium , Aspergillus , and Monascus [ 91 ]. Exposure to CIT is of toxicological interest since it disturbs kidney function in several species, specifically in the renal tubules.…”

“…Exposure to CIT is of toxicological interest since it disturbs kidney function in several species, specifically in the renal tubules. CIT induced micronuclei in human-derived liver cells (HepG2) at levels equal to or greater than 10 μM and decreased in a dose-dependent manner the percentage of binucleated cells [ 91 ]. The Portuguese exposure to CIT was found to be low since it was detected in only 2% of both types of urine samples in median levels of 850 and 750 ng L −1 , for 24-h and first-morning urine samples, respectively.…”