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ARQ 501 (3,4-dihydro-2,2-dimethyl-2H-naphthol[1,2-b]pyran-5,6-dione, beta-lapachone) is an anticancer agent, currently in multiple phase II clinical trials as monotherapy and in combination with other cytotoxic drugs. This study focuses on in vitro metabolism in cryopreserved hepatocytes from mice, rats, dogs and humans using [(14)C]-labeled ARQ 501. Metabolite profiles were characterized using liquid chromatography/mass spectrometry combined with an accurate radioactivity counter. Ion trap mass spectrometry was employed for further structural elucidation. A total of twelve metabolites were detected in the mammalian hepatocytes studied; all of which but one were generated from phase II conjugation reactions. Ten of the observed metabolites were produced by conjugations occurring at the reduced ortho-quinone carbonyl groups of ARQ 501. The metabolite profiles revealed that glucuronidation was the major biotransformation pathway in mouse and human hepatocytes. Monosulfation was the major pathway in dog, while, in rat, it appears glucuronidation and sulfation pathways contributed equally. Three major metabolites were found in rats: monoglucuronide M1, monosulfate M6, and glucuronide-sulfate M9. Two types of diconjugation metabolites were formed by attachment of the second glycone to an adjacent hydroxyl or to an existing glycone. Of the diconjugation metabolites, glucosylsulfate M10, diglucuronide M5, and glucuronide-glucoside M11 represent rarely observed phase II metabolites in mammals. The only unconjugated metabolite was generated through hydrolysis and was observed in rat, dog and human hepatocytes. ARQ 501 appeared less stable in human hepatocytes than in those of other species. To further elucidate the metabolism of ARQ 501 in extrahepatic sites, its metabolism in human kidney, lung and intestine cells was also studied, and only monoglucuronide M1 was observed in all the cell types examined.

ARQ 501 (3,4-dihydro-2,2-dimethyl-2H-naphthol[1,2-b] pyran-5,6-dione), a synthetic version of β-Lapachone, is a promising anti-cancer agent currently in multiple Phase II clinical trials. Promising anti-cancer activity was observed in Phase I and Phase II trials. Metabolism by red blood cells of drugs is an understudied area of research and the metabolites arising from oxidative ring opening (M2 and M3), decarbonylation/ring contraction (M5), and decarbonylation/oxidation (M4 and M6) of ARQ 501 offer a unique opportunity to provide insight into these metabolic processes. Since these metabolites were not detected in in vitro incubations of ARQ 501 with liver microsomes and were structurally diverse, confirmation by chemical synthesis was considered essential. In this report, we disclose the synthetic routes employed and the characterization of the reference standards for these blood metabolites as well as additional postulated structures, which were not confirmed as metabolites.

3,4-Dihydro-2,2-dimethyl-2H-naphthol[1,2-b]pyran-5,6-dione (ARQ 501; beta-lapachone) showed promising anticancer activity in phase I clinical trials as monotherapy and in combination with cytotoxic drugs. ARQ 501 is currently in multiple phase II clinical trials. In vitro incubation in fresh whole blood at 37 degrees C revealed that ARQ 501 is stable in plasma but disappears rapidly in whole blood. Our data showed that extensive metabolism in red blood cells (RBCs) was mainly responsible for the rapid disappearance of ARQ 501 in whole blood. By comparison, covalent binding of ARQ 501 and/or its metabolites to whole blood components was a minor contributor to the disappearance of this compound. Sequestration of intact ARQ 501 in RBCs was not observed. Cross-species metabolite profiles from incubating [(14)C]ARQ 501 in freshly drawn blood were characterized using a liquid chromatography-mass spec-trometry-accurate radioactivity counter. The results show that ARQ 501 was metabolized more rapidly in mouse and rat blood than in dog, monkey, and human blood, with qualitatively similar metabolite profiles. Six metabolites were identified in human blood using ultra-high performance liquid chromatography/time-of-flight mass spectrometry, and the postulated structure of five metabolites was confirmed using synthetic standards. We conclude that the primary metabolic pathway of ARQ 501 in human blood involved oxidation of the two adjacent carbonyl groups to produce dicarboxylic and monocarboxylic metabolites, elimination of a carbonyl group to form a ring-contracted metabolite, and lactonization to produce two metabolites with a pyrone ring to form a ring-contracted metabolite. Metabolism by RBCs may play a role in clearance of ARQ 501 from the blood compartment in cancer patients.

A comparison is presented of product ion mass spectra of protonated and deprotonated molecules of kaempferol-3-O-glucoside, quercitin-3-O-glucoside (isoquercitrin), quercitin-3-O-galactoside (hyperoin), apigenin-7-O-glucoside, luteolin-7-O-glucoside, genistein-7-O-glucoside, naringenin-7-O-glucoside (prunin), luteolin-4′-O-glucoside, luteolin-6-C-glucoside (homoorientin, known also as isoorientin), apigenin-8-C-glucoside (vitexin), and luteolin-8-C-glucoside (orientin) together with the product ion mass spectrum of deprotonated kaempferol-7-O-glucoside. All isomeric ions were distinguishable on the basis of their product ion mass spectra. For protonated 3-O-, 7-O-, and 4′-O-glycosides at a collision energy of 46–47 eV, homolytic cleavage of the O-glycosidic bond yielded aglycon Y + ions, whereas in deprotonated 3-O-, 7-O-, and 4′-O-glycosides, heterolytic and homolytic cleavage of the O-glycosidic bond yielded radical aglycon (Y–H) − and aglycon (Y − ) ions. In each case, fragmentation of either the glycan or the aglycon or both was observed. For 6-C- and 8-C-glycosides at a collision energy of 46–47 eV, fragmentation was restricted almost exclusively to the glycan. For luteolin-6-C-glucoside, the integrity of the aglycon structure is preserved at the expense of the glycan for which some 30 fragmentations were observed. Breakdown curves were determined as a function of collision energy for protonated and deprotonated luteolin-6-C-glucoside. An attempt has been made to rationalize the product ion mass spectra derived from C–O- and C–C-luteolin glucosides in terms of computed structures that indicate significant intramolecular hydrogen bonding and rotation of the B-ring to form a coplanar luteolin structure. It is proposed that protonated and deprotonated luteolin-6-C-glucoside may afford examples of cooperative interactive bonding that plays a major role in directing fragmentation.

Pharmaceutically active compounds (PhACs) are discharged into the environment from domestic wastewater treatment plants (WWTPs). In this study, we determined the distribution of the anti-epileptic drug, carbamazepine (CBZ), and its major metabolites and caffeine in both aqueous and solid phases through different treatment processes of a WWTP. A method was developed to extract samples of biosolids using pressurized liquid extraction (PLE), coupled with cleanup of extracts using solid-phase extraction. Samples of biosolids and wastewater were analyzed for caffeine and CBZ and five of its metabolites, 10,11-dihydro-10,11-epoxycarbamazepine (CBZ-EP), 11-dihydro-10,11-epoxycarbamazepine (CBZ-DiOH), 2-hydroxycarbamazepine (CBZ-20H), 3-hydroxycarbamazepine (CBZ-30H), and 10,11-dihydro-10-hydroxycarbamazepine (CBZ-100H). The analytes were quantified using liquid chromatography-electrospray ionization tandem mass spectrometry. The recoveries of the analytes were 82.1-91.3% from raw biosolids and 80.1-92.4% from treated biosolids, and the limits of detection were 0.06-0.50 and 0.06-0.40 microg/kg on a wet weight basis for raw and treated biosolids, respectively. The behavior of carbamazepine and its metabolites, together with caffeine as a marker of domestic inputs, was investigated in the WWTP for the City of Peterborough, ON, Canada, which utilizes secondary sewage treatment technologies. CBZ, CBZ-2OH, CBZ-30H, and CBZ-DiOH were detected at concentrations of 69.6, 1.9, 1.6, and 7.5 microg/kg (dry weight), respectively, in untreated biosolids and at concentrations of 258.1, 3.4, 4.3, and 15.4 microg/kg (dry weight), respectively, in treated biosolids. However, CBZ-EP and CBZ-100H were not detected in any of the biosolid samples. CBZ and its five metabolites were detected in all wastewater samples collected from four different stages of treatment. The results showed that 29% of the carbamazepine was removed from the aqueous phase during treatment in the WWTP, while the metabolites were not effectively removed. Concentrations of caffeine were reduced by 99.9% in the aqueous phase, which appeared to be due primarily to degradation. Caffeine was also detected at concentrations of 165.8 and 7.6 microg/kg (dry weight) in raw and treated biosolids, respectively. Because of differences in hydrophobicity, CBZ is the primary analyte in biosolids, while CBZ-DiOH is the primary analyte in the aqueous phase of the wastewater. A mass balance calculation showed that the majority of CBZ and its metabolites exist in the aqueous phase (i.e., wastewater), ratherthan in the biosolids, 78 g of CBZ and its metabolites enters the Peterborough WWTP daily, and 91 g is discharged from the WWTP daily in the combined suspended solids and aqueous phases of the wastewater. The calculated daily inputs into the WWTP are somewhat less than the inputs of 192 g estimated from Canadian annual sales data for CBZ.

A mass spectrometric method based on the combined use of electrospray ionization, collision-induced dissociation and tandem mass spectrometry has been applied to the structural characterization of the flavone triglycoside, robinin (3,5,7,4'-tetrahydroxyflavone-3-O-robinoside-7-O-rhamnoside). The deprotonated molecule fragments by loss of the rhamnose glycan residue to yield the Y(7) (-) ion (m/z 593) and by scission of the robinose glycan residue to yield the radical anion [Y(3,0)-H](-.) (m/z 430). The Y(7) (-) ion fragments by scission of the robinose glycan residue to yield the radical anion of Y(7)[Y(3,0)-H](-.) (m/z 284). The [Y(3,0)-H](-.) radical anion fragments by loss of the rhamnose glycan residue to yield the radical anion Y(7)[Y(3,0)-H](-.) (m/z 284) and by scission to yield [Y(7)-H][Y(3,0)--H](-) (m/z 283). A fragmentation mechanism has been proposed.

A mass spectrometric method based on the combined use of electrospray ionization, collision-induced dissociation and tandem mass spectrometry at high mass resolution has been applied to an investigation of the structural characterization of genistein-7-O-β- d -glucoside (5,7,4′-trihydroxyisoflavone). The product ion mass spectrum of [M−H]− ions shows neutral losses of the glycan residue (162 Da) and of the glycan residue + H (163 Da) by rearrangement and scission, respectively, where the latter loss dominates at higher collision energies. The genistein moiety remained intact and only minor fragmentation of the glucose moiety was observed. The low-energy product ion mass spectrum of [M+H]+ ions shows extensive fragmentation of the glucose moiety, though at low ion signal intensity, loss of the glycan residue, and simple fragmentation of the genistein moiety that permits characterization of the substituents in the A and B rings. The use of elevated cone voltages permitted observation of product ion mass spectra of selected primary fragment ions. Product ion mass spectra examined at high mass resolution allowed unambiguous determination of the elemental composition of fragment ions. Fragmentation mechanisms and ion structures have been proposed.

A mass spectrometric method based on the combined use of electrospray ionization, collision-induced dissociation and tandem mass spectrometry at high mass resolution has been applied to an investigation of the structural characterization of protonated and deprotonated kaempferol (3,5,7,4′-tetrahydroxyflavone). Low-energy product ion mass spectra of [M+H]+ ions showed simple fragmentations of the C ring that permitted characterization of the substituents in the A and B rings. In addition, four rearrangement reactions accompanied by losses of C2H2O, CHO, CO, and H2O were observed. Low-energy product ion mass spectra of [M−H]− ions showed only four rearrangement reactions accompanied by losses of OH, CO, CH2O, and C2H2O. The use of elevated cone voltages permitted observation of product ion mass spectra of selected primary and secondary fragment ions so that each fragment ion reported was observed as a direct product of its immediate precursor ion. Product ion mass spectra examined at high mass resolution allowed unambiguous determination of the elemental composition of fragment ions and resolution of two pairs of isobars. Fragmentation mechanisms and ion structures have been proposed.

A mass spectrometric study of three N -oxides, quinoline N -oxide, and the synthetic antibiotics carbadox and olaquindox, was carried out with a hybrid quadrupole/time-of-flight (TOF) mass spectrometer coupled with electrospray (ES) and atmospheric pressure chemical ionization (APCI) sources. The full scan mass spectra of the N -oxides obtained with ES are similar to those obtained with APCI, and the characteristic fragment ions corresponding to [M+H−O] + were observed in the full scan mass spectrum of each N -oxide examined. The protonated molecule of each N -oxide was subjected to collision-induced dissociation (CID) and accurate mass measurements were made of each fragment ion so as to determine its elemental composition. Fragment ions generated at enhanced cone voltages upstream of the first mass-resolving element were subjected to CID so as to identify the direct product ion–precursor ion relationship. Plausible structures have been proposed for most of the fragment ions observed. Elimination of OH radicals generated from the N→O functional group is a characteristic fragmentation pathway of the N -oxides. The expulsion of radicals and small stable molecules is accompanied by formation and subsequent contraction of heterocyclic rings.

A quantitative method is described for solid-phase extraction (SPE) followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the simultaneous analysis of carbamazepine and its five metabolites, 10,11-dihydro-10,11-epoxycarbamazepine, 10,11-dihydro-10,11-dihydroxycarbamazepine, 2-hydroxycarbamazepine, 3-hydroxycarbamazepine, and 10,11-dihydro-10-hydroxycarbamazepine. An SPE procedure was used to concentrate target compounds from aqueous samples collected from sewage treatment plant (STP) wastewater and surface water. Extracts were analyzed using electrospray LC-MS/MS with time-scheduled selected reaction monitoring. The recoveries of the analytes were 83.6-102.2% from untreated sewage (influent), 90.6-103.5% from treated sewage (effluent), and 95.7-102.9% from surface water samples. The instrumental detection limits were 0.8-4.8 pg for the analytes. Matrix effects were investigated for the analytes in HPLC-grade water, surface water, and STP influent and effluent. Ion suppression increased for analytes in order of surface water to STP effluent to STP influent, but no ion suppression was observed for analytes in HPLC-grade water. The developed method was validated by analysis of environmental aqueous samples: STP influent and effluent and surface water. Carbamazepine and all five metabolites were detected in STP influent and effluent samples. Only carbamazepine and 10,11-dihydro-10,11-dihydroxycarbamazepine were detected in the surface water sample. Notably, 10,11-dihydro-10,11-dihydroxycarbamazepine was detected at approximately 3 times higher concentrations than the parent drug, carbamazepine, in all of the aqueous samples. To our knowledge, this is the first report on the simultaneous determination of carbamazepine and its metabolites in environmental samples.

Cholesterol-lowering statin drugs are among the most frequently prescribed agents for reducing morbidity and mortality related to coronary heart disease. Four major statin drugs, atorvastatin, lovastatin, pravastatin and simvastatin, were determined using liquid chromatography–electrospray ionization tandem mass spectrometry with methylammonium acetate as an additive in the mobile phase. Protonated atorvastatin, and methylammonium-adducted lovastatin, pravastatin and simvastatin were selected as precursor ions, and product ions were detected by selected reaction monitoring in positive-ion mode. The instrumental detection limits of atorvastatin, lovastatin, pravastatin and simvastatin are 0.7, 0.7, 8.2 and 0.9 pg, respectively. A solid-phase extraction method was developed to enrich the analytes from aqueous samples. All of the statins were detected in an untreated sewage sample at 4–117 ng/l and in a treated sewage sample at 1–59 ng/l; but only atorvastatin was detected in a surface water sample at 1 ng/l.

Analytical methods were developed for atorvastatin, novobiocin and roxithromycin using microbore liquid chromatography/electrospray ionization tandem mass spectrometry (microbore LC/ESI-MS/MS) in positive and negative voltage switching mode. Atorvastatin and roxithromycin require the positive-ion mode, whereas the negative-ion mode is required for the determination of novobiocin. Using the positive and negative voltage switching function, the three analytes were determined with one injection, and the time required was half that required using separately run positive- and negative-ion modes, without any reduction in sensitivity. A microbore LC column (100 × 1.0 mm i.d.) was chosen for chromatographic separation with mobile phase solvents acetonitrile and 10 mM aqueous ammonium acetate. The flow-rate was 0.1 ml min−1 and the injection volume was 1 µl. The analytes were quantified in the multiple reaction monitoring mode with external standards. By switching the positive and negative voltage, the three analytes were determined with a 4 min chromatographic run and with instrumental detection limits of 1–3 pg. This analytical method, using a microbore LC column combined with solid-phase extraction, was applied successfully to the determination of trace levels of the above pharmaceuticals in aqueous samples. Atorvastatin was detected in a sewage treatment plant final effluent. Copyright © 2003 John Wiley & Sons, Ltd.

The fragmentation pathways of two selected ionophore antibiotics, salinomycin and monensin A, were studied using electrospray (ES) orthogonal acceleration quadrupole time-of-flight mass spectrometry in positive-ion mode. The identity of fragment ions was determined by accurate-mass measurements. In ES mass spectra, ion signals of relatively high intensity were observed for [M+Na](+) and [M-H+2Na](+) for each antibiotic. Each of the ion species [M+Na](+) and [M-H+2Na](+) for salinomycin and [M-H+2Na](+) for monensin A were isolated in turn and subjected to fragmentation. In the fragmentation of [M+Na](+) and [M-H+2Na](+) from salinomycin, only Cbond;C single bond cleavage and dehydration were observed. Product ion mass spectra obtained from [M-H+2Na](+) of monensin A showed that ether ring opening, Cbond;C single bond cleavage and dehydration fragmentations had occurred. Fragment ions containing two sodium atoms were observed in the product ion mass spectrum of [M-H+2Na](+) from salinomycin, but not from monensin A. Both type A (containing the terminal carboxyl group) and type F (containing the terminal hydroxyl group) fragment ions were observed in the product ion mass spectra of sodium adduct ions of salinomycin and monensin A.

Concentrations of arsenic, cadmium, chromium, copper, lead, mercury, selenium, and zinc were measured in coral, crab, eel, fish, lobster, and sediment samples collected from French Frigate Shoals, North Pacific Ocean. The sediments contained relatively high concentrations of selenium; moderate concentrations of arsenic, cadmium, copper and lead; and low concentrations of chromium and zinc. Metal concentrations were also determined in coral and crabs collected from the island of Oahu. Notably, a crab (Grapsus tenuicrustatus) and the undulated moray eel (Gymnothorax undulatus) exhibited high levels of copper and arsenic, respectively, relative to the other species studied. The concentrations of arsenic in the eel averaged 225 microg g(-1) dry wt, which was 3-12 times higher than that in all of the other species tested. The average concentration of copper in the crab was 343 microg g(-1) dry wt, 3-86 times greater than that in the other species studied. These data indicate background and comparative levels of the metals among the studied species. Lead levels in the coral (9-10 microg g(-1) dry wt) and crab (42-57 microg g(-1) dry wt) from Tern and Disappearing Islands were 23-283-fold greater than those from Oahu (0.4 and 0.2 microg g(-1) dry wt, respectively).

3,4-Dihydro-2,2-dimethyl-2H-naphtho[1,2-b]pyran-5,6-dione (ARQ 501) is a fully synthetic version of the natural product beta-lapachone, which has been isolated from the lapacho tree (Tabebuia impetiginosa or Tabebuia avellanedae) and has demonstrated promising anticancer activity. ARQ 501 formulated with hydroxypropyl-beta-cyclodextrin has successfully completed phase I clinical trials and is currently in several phase II human clinical trials for the treatment of pancreatic cancer, head and neck cancer, and leiomyosarcoma. The metabolites of ARQ 501 were investigated by low-resolution and high-resolution mass spectrometry in plasma from (nu/nu) mice, rats, and humans treated with the compound. The data for one of the metabolites identified are consistent with conjugation of ARQ 501 with a glucosylsulfate moiety (m/z 241; fragment ion). Although other glucosylsulfate conjugates have been identified as metabolites of pesticides in cotton plants and in crustaceans as phase II metabolites of pyrenes, none have been previously identified in mammals. Data reported here identify a novel metabolic pathway for humans.

Publisher Summary Pharmaceuticals are used in large quantities throughout the world as prescription and non-prescription drugs. This chapter focuses on the detection of the classes of acidic and neutral drugs in water and wastewater, using liquid chromatography and mass spectrometry (LC-MS and LC-MS/MS) analytical techniques. The chapter outlines the methods for sample collection and storage, sample preparation, LC-MS and LC-MS/MS analysis, matrix effects, and quantification. The development of methods for the analysis of neutral and acidic pharmaceuticals in environmental samples has advanced. However, further advancements are required to address analytical challenges, such as the matrix effects observed with LC-MS/MS analytical techniques. Most of the analytical effort on pharmaceuticals released into the environment is directed at detecting the parent compounds, but more work is required to detect the metabolites of drugs that are excreted by both humans and animals, and transformation products that may be formed during the treatment of water and wastewater. In addition, the analytical techniques to detect pharmaceuticals released as conjugated adducts to biological molecules need to be developed.

To investigate the occurrence of antimicrobials in the final effluents from wastewater treatment plants (WWTPs) in Canada, analytical methods were developed or modified from previously described methods using solid-phase extraction followed by liquid chromatography-electrospray ionization tandem mass spectrometry. Thirty-one antimicrobials from the macrolide, quinolone, quinoxaline dioxide, sulfonamide, and tetracycline classes were investigated in the final (treated) effluents from eight WWTPs, located in five Canadian cities. Ciprofloxacin, clarithromycin, erythromycin-H20, ofloxacin, sulfamethoxazole, sulfapyridine, and tetracycline were frequently detected in the effluents. The detection of sulfapyridine in effluents is the first report of this compound in environmental samples. Antimicrobials used exclusively for veterinary applications or treatment of livestock, such as carbadox, olaquindox, and chlortetracycline were not detected in the WWTP final effluents. There appear to be differences in the relative concentrations of antimicrobials detected in WWTP final effluents in Canada relative to concentrations reported previously in northern Europe, particularly for quinolone and sulfonamide compounds. These data may reflect differences in prescription patterns in Canada and northern Europe. The antimicrobials frequently detected in WWTP effluents appear to be those prescribed heavily in Canada for medical applications, and these compounds should be considered priority compounds for monitoring in surface water near WWTP discharges. The concentrations of antimicrobials detected in WWTP final effluents did not exceed 1 microg/L; levels that are unlikely to affect the growth and survival of aquatic organisms.

Ginsenosides R(b1), R(b2), R(c), R(d), R(e), R(f), R(g1), R(g2) and F(11) were studied systematically by electrospray ionization mass spectrometry in positive- and negative-ion modes with a mobile-phase additive, ammonium acetate. In general, ion sensitivities for the ginsenosides were greater in the negative-ion mode, but more structural information on the ginsenosides was obtained in the positive-ion mode. [M + H](+), [M + NH(4)](+), [M + Na](+) and [M + K](+) ions were observed for all of the ginsenosides studied, with the exception of R(f) and F(11), for which [M + NH(4)](+) ions were not observed. The signal intensities of [M + H](+), [M + NH(4)](+), [M + Na](+) and [M + K](+) ions varied with the cone voltage. The highest signal intensities for [M + H](+) and [M + NH(4)](+) ions were obtained at low cone voltage (15-30 V), whereas those for [M + Na](+) and [M + K](+) ions were obtained at relatively high cone voltage (70-90 V). Collision-induced dissociation yielded characteristic positively charged fragment ions at m/z 407, 425 and 443 for (20S)-protopanaxadiol, m/z 405, 423 and 441 for (20S)-protopanaxatriol and m/z 421, 439, 457 and 475 for (24R)-pseudoginsenoside F(11). Ginsenoside types were identified by these characteristic ions and the charged saccharide groups. Glycosidic bond cleavage and elimination of H(2)O were the two major fragmentation pathways observed in the product ion mass spectra of [M + H](+) and [M + NH(4)](+). In the product ion mass spectra of [M - H](-), the major fragmentation route observed was glycosidic bond cleavage. Adduct ions [M + 2AcO + Na](-), [M + AcO](-), [M - CH(2)O + AcO](-), [M + 2AcO](2-), [M - H + AcO](2-) and [M - 2H](2-) were observed at low cone voltage (15-30 V) only.

A liquid chromatography–electrospray ionization tandem mass spectrometry (LC–ESI-MS–MS) method was developed and validated for simultaneous analysis of nine acidic pharmaceutical drugs (bezafibrate, clofibric acid, diclofenac, fenoprofen, gemfibrozil, ibuprofen, indomethacin, ketoprofen and naproxen) in sewage treatment plant (STP) effluents. The mean recoveries of the pharmaceuticals ranged from 58.9 to 91.5% in STP effluent, and the limits of detection of the analytes were 5–20 ng/ml. The method was applied to the quantitative analysis of acidic drugs in the effluents from three Canadian STPs, in which bezafibrate, diclofenac, fenoprofen, gemfibrozil, ibuprofen, indomethacin and naproxen were detected.

Chemical pollution may play a role in the etiology of fibropapillomatosis in green turtles (Chelonia mydas). In this preliminary study, polychlorinated biphenyls (PCBs) were measured in the livers and adipose fats of green turtles collected after they were stranded on Oahu Island, Hawaii in 1992-1993. Average concentrations of total PCBs were 45-58 ng/g dry weight and 73-665 ng/g in the liver and adipose tissues, respectively. Hexachlorobiphenyls were predominant homologues, PCBs 153 and 138 were dominant congeners in all the turtle tissues. Among the most toxic coplanar congeners, in the order of abundance, were PCB 77 > 126 > 169. Estimated toxic equivalents (TEQs) of PCBs to 2,3,7,8-tetrachlorodibenzo-p-dioxin were 8-15 pg/g in the livers and 13-48 pg/g in the adipose tissues. PCB 126 contributed 85-91% of the total TEQs.

Polychlorinated biphenyls (PCBs) were analyzed in: sediment; coral ( Porites evermanni ); fish ( Stegastes fasciolatus , Neoniphon sammara , Acanthurus triostegus and Mulloidichthys vanicolensis ); crab ( Grapsus tenuicrustatus ); lobster ( Panulirus marginatus ); and eel ( Conger cinereus , Gymnothorax flavimarginatus , G. undulatus and G. meleagris ) samples collected from Tern Island and the corresponding reference samples from Disappearing Island. The two islands are part of French Frigate Shoals, a national wildlife refuge in the North Pacific Ocean. The dominant congeners 118, 138 and 153 represent 22–25, 32–34, 12–39, 37–46 and 30–55% of the sum of PCBs in the coral, sediment, fish, crab and eel, respectively. In general, high trophic species such as eels were found to highly bioaccumulate PCBs. The total average PCB concentrations were as high as 96 and 29 μg/g dry wt. in eels and damselfish, respectively, from Tern Island. The localized behavior and high bioaccumulation potential for PCBs suggest that damselfish are an excellent species for monitoring PCBs in small areas in the ocean. The high average concentrations of the sum of PCBs in different food chain levels suggest that pollution source(s) are around Tern Island and possibly around Disappearing Island. Aroclor 1254 and its analogs are suspected sources responsible for PCBs in the samples.

Prescription and nonprescription drugs have been detected in rivers and streams in Europe and the United States. Sewage treatment plants (STPs) are an important source of these contaminants, but few data exist on the spatial distribution of drugs in surface waters near STPs. Samples of surface water were collected in the summer and fall of 2000 at open-water sites in the lower Great Lakes (Lake Ontario and Lake Erie), at sites near the two STPs for the city of Windsor (ON, Canada), and at sites in Hamilton Harbour (ON, Canada), an embayment of western Lake Ontario that receives discharges from several STPs. In a follow-up study in the summer of 2002, samples of surface water and final effluent from adjacent STPs were collected from sites in Hamilton Harbour and Windsor. In addition, surface water and STP effluent samples were collected in Peterborough (ON, Canada). All samples of surface water and STP effluents were analyzed for selected acidic and neutral drugs. In the survey of Hamilton Harbour and Windsor conducted in 2000, acidic drugs and the antiepileptic drug carbamazepine were detected at ng/L concentrations at sites that were up to 500 m away from the STP, but the hydrological conditions of the receiving waters strongly influenced the spatial distribution of these compounds. Drugs were not detected at open-water locations in western Lake Erie or in the Niagara River near the municipality of Niagara-on-the-Lake (ON, Canada). However, clofibric acid, ketoprofen, fenoprofen, and carbamazepine were detected in samples collected in the summer of 2000 at sites in Lake Ontario and at a site in the Niagara River (Fort Erie, ON, Canada) that were relatively remote from STP discharges. Follow-up studies in the summer of 2002 indicated that concentrations of acidic and neutral drugs in surface waters near the point of sewage discharge into the Little River (ON, Canada) STP were approximately equal to the concentrations in the final effluent from the STP. Caffeine and cotinine, a metabolite of nicotine, were generally present in STP effluents and surface waters contaminated by drugs. The antidepressant fluoxetine and the antibiotic trimethoprom were also detected in most STP effluents and some surface water samples. For the first time, the lipid regulating drug atorvastatin was detected in samples of STP effluent and surface water.