Contemporary and Historical Atmospheric Deposition of Arsenic and Selenium in the Athabasca Bituminous Sands Region.

Selenium (Se) is one of the trace elements that is enriched in bitumen. To assess the importance of atmospheric Se deposition from mining and upgrading of bituminous sands in northern Alberta, Canada, Sphagnum moss was obtained from 25 bogs near industrial operations. The average Se concentration in moss near industries (58 ± 13 µg/kg; n = 75) was greater than in remote sites in Alberta (29-50 µg/kg), but comparable to bogs in central regions of the province and lower than bogs in southern Ontario (121-244 µg/kg) or the west and east coasts (230-285 µg/kg). In bog vegetation and peat, arsenic (As) concentrations and accumulation rates are 10 times greater at the industrial site (MIL) compared to the control site (UTK), but this is proportional to the differences in scandium (a surrogate for mineral matter concentrations), which points to dust as the predominant As source. An age-dated peat core collected near industries revealed that both Se and As deposition have declined in recent years. A peat core from UTK provided a record of atmospheric deposition dating back over 2700 years, indicating that As and Se deposition in northern Alberta increased considerably in the early 19th century and then went into decline during ∼1950-1970.

Peat Bogs Document Decades of Declining Atmospheric Contamination by Trace Metals in the Athabasca Bituminous Sands Region.

Peat cores were collected from five bogs in the vicinity of open pit mines and upgraders of the Athabasca Bituminous Sands, the largest reservoir of bitumen in the world. Frozen cores were sectioned into 1 cm slices, and trace metals determined in the ultraclean SWAMP lab using ICP-QMS. The uppermost sections of the cores were age-dated with 210Pb using ultralow background gamma spectrometry, and selected plant macrofossils dated using 14C. At each site, trace metal concentrations as well as enrichment factors (calculated relative to the corresponding element/Th ratio of the Upper Continental Crust) reveal maximum values 10 to 40 cm below the surface which shows that the zenith of atmospheric contamination occurred in the past. The age-depth relationships show that atmospheric contamination by trace metals (Ag, Cd, Sb, Tl, but also V, Ni, and Mo which are enriched in bitumen) has been declining in northern Alberta for decades. In fact, the greatest contemporary enrichments of Ag, Cd, Sb, and Tl (in the top layers of the peat cores) are found at the control site (Utikuma) which is 264 km SW, suggesting that long-range atmospheric transport from other sources must be duly considered in any source assessment.

Airborne Petcoke Dust is a Major Source of Polycyclic Aromatic Hydrocarbons in the Athabasca Oil Sands Region.

Oil sands mining has been linked to increasing atmospheric deposition of polycyclic aromatic hydrocarbons (PAHs) in the Athabasca oil sands region (AOSR), but known sources cannot explain the quantity of PAHs in environmental samples. PAHs were measured in living Sphagnum moss (24 sites, n = 68), in sectioned peat cores (4 sites, n = 161), and snow (7 sites, n = 19) from ombrotrophic bogs in the AOSR. Prospective source samples were also analyzed, including petroleum coke (petcoke, from both delayed and fluid coking), fine tailings, oil sands ore, and naturally exposed bitumen. Average PAH concentrations in near-field moss (199 ng/g, n = 11) were significantly higher (p = 0.035) than in far-field moss (118 ng/g, n = 13), and increasing temporal trends were detected in three peat cores collected closest to industrial activity. A chemical mass-balance model estimated that delayed petcoke was the major source of PAHs to living moss, and among three peat core the contribution to PAHs from delayed petcoke increased over time, accounting for 45-95% of PAHs in contemporary layers. Petcoke was also estimated to be a major source of vanadium, nickel, and molybdenum. Scanning electron microscopy with energy-dispersive X-ray spectroscopy confirmed large petcoke particles (>10 µm) in snow at near-field sites. Petcoke dust has not previously been considered in environmental impact assessments of oil sands upgrading, and improved dust control from growing stockpiles may mitigate future risks.

Blood Bag Plasticizers Influence Red Blood Cell Vesiculation Rate without Altering the Lipid Composition of the Vesicles.

BACKGROUND: Polyvinyl chloride (PVC) plasticized with di(2-ethylhexyl) phthalate (DEHP) is commonly used for blood collection and storage. DEHP has protective effects on RBC membranes, but is also a toxin. METHODS: A paired study was conducted to investigate the influence of DEHP and two alternative plasticizers, 1,2-cyclohexane-dicarboxylic acid diisononyl ester (DINCH) and n-butyryl-tri-n-hexyl citrate (BTHC), on the preservation of RBCs stored for 42 days in PVC pediatric bags. The RBC membrane was evaluated for supernatant hemoglobin (Hb), release of extracellular microvesicles (EVs), osmotic fragility, deformability, and lipid composition. RESULTS: In BTHC-plasticized bags, the supernatant Hb increase during storage was 2 times greater than in DINCH- and DEHP-plasticized bags. By day 21, EV concentrations had doubled from day-5 levels in DINCH- and DEHP-, and trebled in BTHC-plasticized bags. RBC mean cell volumes were greater in BTHC- than in DINCH- or DEHP-plasticized bags (p < 0.001). Osmotic fragility differed significantly among plasticizers (p < 0.01). After day 21, RBC deformability decreased in all, but to a greater extent in the bags with BTHC. Phospholipid composition of RBCs and EVs was not different among plasticizers. CONCLUSION: Membrane stabilization capacity differed among the plasticizers. RBC in BTHC bags stored more poorly, while DEHP and DINCH bags offered better protection against vesiculation, osmotic stress, and Hb loss.

Phospholipidomics reveals differences in glycerophosphoserine profiles of hypothermically stored red blood cells and microvesicles.

During their normal in vivo life cycle erythrocytes (red blood cells, RBCs) undergo biochemical changes leading to membrane microvesiculation and shedding. RBC microvesiculation also occurs in vitro under conditions of blood bank storage, so microvesicles (MVs) accumulate in the storage (preservation) medium over storage time. Considerable effort has been put into gaining a mechanistic understanding of the RBC microvesiculation process, as this is crucial to better understand RBC biology in disease and in health. Additionally, MVs accumulated in stored RBCs have been implicated in transfusion adverse inflammatory reactions, with chloroform extractable compounds, thus lipophilic, known to trigger the effect. However, because thin layer chromatography resolution of RBC and MV lipids has always enabled one to conclude high compositional similarities, in depth analysis of MV lipids has not been extensively pursued. Here we present an orbitrap mass spectrometry (MS) approach to compare the phospholipid composition of RBCs and MVs from leukoreduced, hypothermically (2-6°C) stored RBC units. We used shotgun MS analysis and electrospray ionization (ESI) intra-source separation, and demonstrated high similarity of compositional profiles, except for glycerophosphoserines (PS). Contrasting abundances of PS 38:4 and PS 38:1 characterized MV and RBC profiles and suggested that storage-associated microvesiculation possibly involves shedding of specific membrane rafts. This finding indicates that phospholipidomics could likely contribute to a better understanding of the RBC microvesiculation process.

The effects of rejuvenation during hypothermic storage on red blood cell membrane remodeling.

BACKGROUND: Our previous studies showed that hypothermic storage (HS) induces red blood cell (RBC) microparticle (RMP) generation and changes in phosphatidylserine (PS) and CD47 expression on RBCs and RMPs. The aim of this study was to evaluate the effect of cold rejuvenation treatment at multiple time points during storage on these prehemolytic indicators of RBC membrane storage lesion. STUDY DESIGN AND METHODS: Leukoreduced RBC units in saline-adenine-glucose-mannitol were used to generate three groups: untreated controls, sham-treated units, and units treated with a cold (1-6°C) rejuvenation solution on Day 28, 35, or 42 of HS. Units were assessed for hemolysis, adenosine triphosphate (ATP) concentration, lipid composition, and RMP generation, as well as PS and CD47 expression throughout 49 days of HS. RESULTS: Rejuvenation treatment led to a significant increase in ATP concentration in all units, irrespective of treatment day. There were no significant differences between sham- and rejuvenation-treated RBC samples in the levels of PS externalization, CD47 expression, or the rate of RMP formation. RBCs rejuvenated on Day 28 were enriched in glycerophosphocholine (+23.5%), depleted in sphingomyelin (-14%), and slightly depleted in cholesterol (-3.5%). CONCLUSION: Cold rejuvenation in hypothermically stored RBCs affects the lipid composition of RBCs and respective RMPs in a time-dependent fashion.

A geochemical perspective on the natural abundance and predominant sources of trace elements in cranberries (Vaccinium oxycoccus) from remote bogs in the Boreal region of northern Alberta, Canada.

Trace elements in native cranberry (Vaccinium oxycoccus) were compared with the underlying Sphagnum moss on which it grows, from two remote ombrotrophic (rain-fed) peat bogs in northern Alberta, Canada. The purpose of the comparison was to distinguish between dust inputs to the berries versus plant uptake from the substrate, and to determine the natural abundance of trace elements in native berries. Using Al as an indicator of the abundance of soil-derived mineral particles, the abundance of dust on the surface of the berries is 20 to 29× lower than that of the substrate (moss). Other lithophile elements (V, Cr, Co, Ga, Li and Y) show similar differences between moss and berry. The concentrations of Rb and Ba in berries were similar to moss and Sr within a factor of 3 to 4×, probably reflecting passive uptake of these lithophile elements by the plants, even though they have no known physiological function. Of the micronutrients examined (Mn, Fe, Ni, Cu, Zn and Mo), Cu and Mn were more abundant in berries than moss, Ni and Zn yielded similar concentrations in both whereas Fe followed by Mo showed the greatest concentration difference. For these micronutrients, uptake by the plants through their roots via the substrate (moss and peat) outweighs contributions from atmospheric dusts. In respect to potentially toxic "heavy metals", Pb concentrations in the moss (BMW, 89 ±â€¯7.3 µg/kg; CMW, 93 ±â€¯27 µg/kg) are below the natural, "background" values reported for ancient layers of Swiss peat from the mid-Holocene (>6000 years old). The Pb concentrations in the berries, however, are 19 to 47× lower than in the underlying moss indicating that Pb in the berries, like Al, is exclusively supplied by dust. Cadmium in the berries is at or above the level found in moss due to active uptake by the plants from the substrate, most likely because of the chemical similarity of this element to Zn. Silver, Sb and Tl in the berries were

Trace elements in berries collected near upgraders and open pit mines in the Athabasca Bituminous Sands Region (ABSR): Distinguishing atmospheric dust deposition from plant uptake.

There are ongoing concerns regarding environmental emissions of trace elements (TEs) from bitumen mining and upgrading in the Athabasca Bituminous Sands Region (ABSR). Depending on their physical and chemical forms, elevated concentrations of potentially toxic TEs in berries could pose a health risk to local indigenous communities because native fruits are an important part of their traditional diet. The objective of this study was to distinguish between aerial deposition of TEs versus plant uptake, in cranberries, lingonberries, and blueberries growing in the ABSR. The concentrations of TEs were determined using ICP-MS in the metal-free, ultraclean SWAMP lab at the University of Alberta. The spatial variation in abundance of conservative, lithophile elements such as Y in berries resembles the published map of dust deposition rates obtained using Sphagnum moss. The presence of dust particles on the surface of the berries near open pit mines and upgraders was confirmed using SEM. Elements which show strong, positive correlation with Y include Al, Cr, Pb, U, and V; these are supplied mainly by dust. Elements which are largely independent of Y concentrations include Ba, Cd, Cu, Mn, Mo, Ni, Rb, Sr, and Zn; these are obtained primarily by plant uptake from soil. The concentrations of elements associated with dust were considerably reduced after washing with water, but the elements independent of dust inputs were unaffected. Elements which are supplied almost exclusively by dust (e.g. Y) are more abundant in berries from the ABS region (2 to 24 times), compared to berries from remote locations.

A geochemical perspective on the natural abundance of trace elements in beaver (Castor canadensis) from a rural region of southern Ontario, Canada.

Chalcophile (Ag, Cd, Co, Cu, Mo, Ni, Pb, Se, Tl, Zn) and lithophile (Al, Ba, Ce, Cr, Cs, Fe, La, Li, Mn, Nd, Rb, Sr, V, Y) trace elements (TEs) were determined in kidney, liver and muscle of beaver (Castor canadensis) from a rural watershed in southern Ontario, Canada. To estimate the relative bioavailability of TEs in the landscape, they were also determined in the dissolved (<0.45 µm) fraction of water from the river where the animals were harvested. Concentration ratios (tissue/water) always showed the greatest enrichments for Cd (kidney, 1.1 × 107; liver, 2.4 × 106; muscle, 7.2 × 105), most likely due to the metal binding properties of metallothioneins. Despite its potential toxicity, Tl also showed considerable enrichment: kidney, 4.2 × 104; liver 1.2 × 104; muscle 1.5 × 104. Enrichments of Cs and Rb exceeded those of Tl in all three tissues, suggesting that the chemical similarity of their ionic species (Cs+, Rb+, Tl+) to K+ may be the key to their uptake. Lithophile elements of limited solubility in natural waters (Al, Ce, La, Nd) show moderate enrichments, despite the lack of physiological role. The smallest enrichments were found for Sr and Ba, the two TEs which are most abundant in the river. Of the TEs considered essential for animal nutrition, V was the least enriched in tissue relative to water (liver 19×, kidney, 33× and muscle 28×). Despite the lack of physiological function and absence of any known sources of contamination, Al, Ag, Cd, Ce, Cs, La, Pb, Rb, and Tl, are all enriched in beaver tissue, relative to water, by at least three orders of magnitude, due to natural processes. The widespread abundance of beaver in Canada combined with the growing need to manage their numbers in populated regions offer a unique opportunity for monitoring environmental quality in the riparian zone.

Bioaccumulation of Tl in otoliths of Trout-perch (Percopsis omiscomaycus) from the Athabasca River, upstream and downstream of bitumen mining and upgrading.

It has been suggested that open pit mining and upgrading of bitumen in northern Alberta releases Tl and other potentially toxic elements to the Athabasca River and its watershed. We examined Tl and other trace elements in otoliths of Trout-perch (Percopsis omiscomaycus), a non-migratory fish species, collected along the Athabasca River. Otoliths were analyzed using ICP-QMS, following acid digestion, in the metal-free, ultraclean SWAMP laboratory. Compared to their average abundance in the dissolved (<0.45 µm) fraction of Athabasca River, Tl showed the greatest enrichment in otoliths of any of the trace elements, with enrichments decreasing in the order Tl, Sr, Mn, Zn, Ba, Th, Ni, Rb, Fe, Al, Cr, Ni, Cu, Pb, Co, Li, Y, V, and Mo. Normalizing Tl in the otoliths to the concentrations of lithophile elements such as Li, Rb, Al or Y in the same tissue reveals average enrichments of 177, 22, 19 and 190 times, respectively, relative to the corresponding ratios in the water. None of the element concentrations (Tl, Li, Rb, Al, Y) or ratios were significantly greater downstream of industry compared to upstream. This natural bioaccumulation of Tl most likely reflects the similarity in geochemical and biological properties of Tl+ and K+. SUMMARY OF MAIN FINDINGS: Thallium is enriched in fish otoliths, relative to the chemical composition of the river, to the same degree both upstream and downstream of industry.

Spatial assessment of major and trace element concentrations from Lower Athabasca Region Trout-perch (Percopsis omiscomaycus) otoliths.

The Lower Athabasca Region (LAR) is home to the largest bitumen deposit in Alberta, and has seen industrial development related to the extraction and processing of bituminous sands since the late 1960s. Along with industrial and economic growth related to oil sands development, environmental concerns have increased in recent decades, including those about potential effects on fish. We measured major and trace element concentrations in Trout-perch otoliths from the Athabasca and Clearwater Rivers in the LAR, to illustrate spatial variations and identify possible industrial impacts. Both laser ablation ICP-MS and solution-based ICP-MS methods were employed. Of the trace elements enriched in bitumen (V, Ni, Mo and Re), only Ni and Re were above the limits of detection using at least one of the methods. The only significant differences in element concentrations between upstream and downstream locations were found for Li, Cu, and Pb which were more abundant upstream of industry. For comparison and additional perspective, otoliths from the same fish species, but taken from the Batchawana River in northern Ontario, were also examined. The fish from Alberta yielded greater concentrations of Ba, Bi, Li, Mg, Na, Re, Sc, Th and Y, but the Ontario fish had more Cr, Rb and Tl, likely because of differences in geology.

Creating a fatty acid methyl ester database for lipid profiling in a single drop of human blood using high resolution capillary gas chromatography and mass spectrometry.

Capillary gas chromatography (CGC) in combination with mass spectrometry (MS) was optimized for the separation and detection of the fatty acids occurring in the lipid fraction of blood. A fingertip blood sample (ca. 50 microL) was transesterified into the methyl esters and analyzed on a 100 m x 0.25 mm ID column coated with a biscyanopropyl polysiloxane (HP-88) stationary phase. The method was retention time locked. Programmed temperature vaporization injection (PTV) in the solvent venting mode was applied to minimize the sample size, while maintaining high sensitivity. The total analysis time was ca. 60 min. Retention times and both electron impact (EI) and positive chemical ionization (PCI) mass spectrometry were combined to elucidate the fatty acids according to alkyl chain, degree of unsaturation and position of the double bonds. Using extracted ion chromatograms about 100 fatty acids and related compounds were detected in blood samples and most of them were identified. This work resulted in a very large fatty acid methyl esters database, containing retention time and mass spectral information that will be applied to metabolomic studies.

Analysis of dihydropyridine calcium channel blockers using negative ion photoionization mass spectrometry.

The fragmentation of dihydropyridine calcium-channel antagonists are compared by electrospray ionization (ESI) and atmospheric pressure photonization (APPI). The results demonstrate that in ESI the preferred ionization process is in positive mode, with the mass spectra of [M+H]+ showing base peak ions probably formed by loss of alcohols from carboxyl groups. Conversely, in APPI, a high intense peak is observed in negative mode due to deprotonated molecule [M-H]- after two serial 1, 2-hydride shifts leading to a rearranged deprotonated molecule [M-H]-. These ions undergo another 1,2-hydride shifts to produce a nitro-phenyl product ion of m/z 122. The APPI is also used to develop a method for the quantitation of dihydropyridines (e.g., nifedipine) in human plasma.

Trace metals in the dissolved fraction (<0.45µm) of the lower Athabasca River: Analytical challenges and environmental implications.

Water samples were collected on the Athabasca River (AR), upstream and downstream from bitumen mines and upgrading facilities, to identify changes in water quality due to industrial activities in this region of northern Alberta, Canada. Starting upstream of Fort McMurray and proceeding downstream ca. 100km, waters were collected in duplicate at 13 locations on the main stem of the river, as well as 5 tributary streams, using ultraclean sampling protocols developed for polar snow and ice. To estimate potential bioaccessibility, trace elements of concern (Ag, Cd, Pb, Sb, Tl) were determined in the dissolved fraction (<0.45µm) along with metals known for their enrichments in bitumen (V, Ni, Mo, Re) and those found mainly in ionic (Li, Sr) or colloidal forms (Al, Co, Cr, Fe, Ga, Mn, Th, Y). Analyses were performed in the metal-free, ultraclean SWAMP lab using quadrupole and sector-field ICP-MS. Concentrations of Ag, Cd, Pb, Sb and Tl were extremely low, not significantly more abundant downstream of industry and probably reflect "background" values. In contrast, V, Ni, Mo and Re concentrations were all significantly (p<0.05) greater downstream of industry. However, chloride also increased downstream, due to natural inputs of saline groundwaters and it is unclear whether the increases in V, Ni, Mo and Re are due to natural or anthropogenic inputs to the river. Although it had been claimed that the industrial development of the Athabasca Bituminous Sands (ABS) is a significant source of Ag, Cd, Pb, Sb and Tl to the river, our study failed to find any evidence to support this. Here we provide a first, robust (accurate and precise) description of baseline values for these trace elements in the AR, and suggest that V, Ni, Mo and Re are more valuable tracers for environmental monitoring and source assessment.

Dust is the dominant source of "heavy metals" to peat moss (Sphagnum fuscum) in the bogs of the Athabasca Bituminous Sands region of northern Alberta.

Sphagnum fuscum was collected from twenty-five ombrotrophic (rain-fed) peat bogs surrounding open pit mines and upgrading facilities of Athabasca Bituminous Sands (ABS) in northern Alberta (AB) in order to assess the extent of atmospheric contamination by trace elements. As a control, this moss species was also collected at a bog near Utikuma (UTK) in an undeveloped part of AB and 264km SW of the ABS region. For comparison, this moss was also collected in central AB, in the vicinity of the City of Edmonton which is approximately 500km to the south of the ABS region, from the Wagner Wetland which is 22km W of the City, from Seba Beach (ca. 90km W) and from Elk Island National Park (ca. 45km E). All of the moss samples were digested and trace elements concentrations determined using ICP-SMS at a commercial laboratory, with selected samples also analyzed using instrumental neutron activation analysis at the University of Alberta. The mosses from the ABS region yielded lower concentrations of Ag, As, Bi, Cd, Cu, Pb, Sb, Tl, and Zn compared to the moss from the Edmonton area. Concentrations of Ni and Mo in the mosses were comparable in these two regions, but V was more abundant in the ABS samples. Compared with the surface vegetation of eight peat cores collected in recent years from British Columbia, Ontario, Quebec and New Brunswick, the mean concentrations of Ag, As, Bi, Cd, Cu, Mo, Ni, Pb, Sb, Tl and Zn in the mosses from the ABS region are generally much lower. In fact, the concentrations of these trace elements in the samples from the ABS region are comparable to the corresponding values in forest moss from remote regions of central and northern Norway. Lithophile element concentrations (Ba, Be, Ga, Ge, Li, Sc, Th, Ti, Zr) explain most of the variation in trace metal concentrations in the moss samples. The mean concentrations of Th and Zr are greatest in the moss samples from the ABS region, reflecting dust inputs to the bogs from open pit mines, aggregate quarries, and gravel roads. Linear regressions of V, Ni, and Mo (elements enriched in bitumen) versus Sc (a conservative, lithophile element) show excellent correlations in the mosses from the ABS region, but this is true also of Ag, Pb, Sb and Tl: thus, most of the variation in the trace metal concentrations can be explained simply by the abundance of dust particles on the plants of this region. Unlike the moss samples from the ABS region and from UTK where Pb/Sc ratios resemble those of crustal rocks, the moss samples from the other regions studied yielded much greater Pb/Sc ratios implying significant anthropogenic Pb contributions at these other sites.

Pharmacokinetics of dihydroergocristine and its major metabolite 8'-hydroxy-dihydroergocristine in human plasma.

Dihydroergocristine (DHEC) is a semi-synthetic drug mainly used for age-related cognitive impairment. In this study, its major metabolite 8'-hydroxy-dihydroergocristine (8'-OH-DHEC) was produced in incubates of a bovine liver preparation using dihydroergocristine mesylate (DHECM) as substrate. Purification was achieved by flash silica gel column and reverse phase liquid chromatographies, and identification was based on accurate molecular mass measurements, mass fragmentation spectra and NMR ((1)H/(13)C) chemical shifts. By using the substance produced in vitro, a fast, sensitive, specific and robust LC/MS/MS method for the simultaneous determination of DHEC and its major metabolite in human plasma was developed and validated. Bromocriptine was used as internal standard and limits of quantification for DHEC and 8'-OH-DHEC were 10 pg/ml and 20 pg/ml, respectively. Pharmacokinetic parameters were investigated on 12 male healthy volunteers to whom a single dose of 18 mg DHECM was administered in tablets (Iskevert). The peak of DHEC was 0.28 +/- 0.22 microg/l, the t(max) 0.46 +/- 0.26 h, the AUC(last) 0.39 +/- 0.41 microg/l.h and the terminal elimination half-life 3.50 +/- 2.27 h. The peak of 8'-OH-DHEC was 5.63 +/- 3.34 microg/l, the t(max) 1.04 +/- 0.66 h, the AUC(last) 13.36 +/- 5.82 microg/l.h and the terminal elimination half-life 3.90 +/- 1.07 h. Dosing of 18 mg DHECM was well tolerated, causing no adverse events.

Antimicrobial compounds of fungi vectored by Clusia spp. (Clusiaceae) pollinating bees.

The production of antimicrobial compounds by fungi associated with Clusia spp. pollinating bees (Trigona sp., Trigonini) was investigated in order to approach natural mechanisms of microbial density control within nest environment. By using a bioassay-guided approach based on bioautography and minimal inhibitory concentration (MIC), known alpha,beta-dehydrocurvularin and curvularin were isolated from Curvularia eragrostidis (CCT 5634) and Curvularia pallescens (CCT 5654), and known cochlioquinone A and isocochlioquinone A were isolated from Drechslera dematioidea (CCT 5631).

Identification and human pharmacokinetics of dihydroergotoxine metabolites in man: preliminary results.

Dihydroergotoxine is a mixture of semi-synthetic ergot alkaloids mainly used for age-related cognitive impairment. In this study, dihydroergotoxine (30 microM) was added to incubates of rat and bovine liver microsomes, and the resulting major metabolites were identified as hydroxy-dihydroergocornine, hydroxy-dihydroergocryptine and hydroxy-dihydroergocristine on the basis of molecular mass measurements, determined with a time-of-flight mass spectrometer. The relevance of these to humans was then investigated by simultaneously monitoring dihydroergotoxine and its hydroxy-metabolites in human plasma by LC-MS/MS after oral dosing of dihydroergotoxine mesylate (27 mg) to a healthy volunteer (male, age 45, height 1.93 m, weight 103 kg). In this preliminary approach, the peaks (C(max)) of dihydroergocornine, dihydroergocryptine and dihydroergocristine were about 0.04 microg/l. The peaks (C(max)) of their hydroxy-metabolites were 0.98, 0.53 and 0.30 microg/l, respectively. In conclusion, in this preliminary approach it was found that hydroxy-dihydroergocornine, hydroxy-dihydroergocryptine and hydroxy-dihydroergocristine were one order of magnitude higher in concentration than their parents in human plasma.