Atropisomeric determination of chiral hydroxylated metabolites of polychlorinated biphenyls using HPLC-MS

Chemistry Central Journal

Guangshu Zhai²  Xianai Wu¹  Hans-Joachim Lehmler¹  Jerald L Schnoor¹ 

[1] Department of Occupational and Environmental Health, The University of Iowa, Iowa City 52242, IA, USA

[2] Department of Civil and Environmental Engineering and IIHR Hydroscience and Engineering, The University of Iowa, Iowa City 52242, IA, USA

关键词: Rat liver microsome;    HPLC-MS;    Hydroxylated metabolites;    Chiral polychlorinated biphenyls;   

Others  :  787811
DOI  :  10.1186/1752-153X-7-183

 received in 2013-09-25, accepted in 2013-12-16,  发布年份 2013

【 摘 要 】

Background

Polychlorinated biphenyls (PCBs) are a group of environmental persistent organic pollutants, which can be metabolized into a series of metabolites, including hydroxylated metabolites (OH-PCBs) in biota. Nineteen of 209 PCB congeners can form chiral stable isomers. However, atropisomeric determination of the hydroxylated metabolites of these chiral PCBs has never been reported by LC methods. In this work, a novel HPLC-MS method was developed to detect five chiral OH-PCBs (4OH-PCB91, 5OH-PCB91, 4OH-PCB95, 5OH-PCB95 and 5OH-PCB149) using HPLC-MS without a derivatization step.

Results

The influences of column-type, column temperature, flow rate and ratio of the mobile phase on the atropisomeric separation were investigated in detail. In the final method, calibration curves, based on peak areas against concentration, were linear in a range of 1–100 ng mL^-1 of five chiral OH-PCBs with correlation coefficients ranging from 0.9996 to 0.9999 for all atropisomers of OH-PCBs. The relative standard deviations measured at the 10.0 ng mL^-1 level for atropisomers of five chiral OH-PCBs were in the range of 0.60-7.55% (n = 5). Calculated detection limits (S/N = 3) of five chiral OH-PCBs were between 0.31 and 0.60 ng mL^-1 for all OH-PCB atropisomers.

Conclusion

This HPLC-MS method was developed to detect chiral OH-PCBs and further successfully applied to measure OH-PCB atropisomer levels and enantiomeric fractions (EFs) in rat liver microsomal samples. The results from LC-MS method were highly consistent with those from GC-ECD method. It is the first time to report these OH-PCB atropisomers detected in microsomes by HPLC-MS. The proposed method might be applied also to detect chiral OH-PCBs in environmental samples and for metabolites of PCBs in vivo.

【 授权许可】

   
2013 Zhai et al.; licensee Chemistry Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

【 参考文献 】

• [1]Safe SH: Polychlorinated biphenyls (PCBs): environmental impact, biochemical and toxic responses, and implications for risk assessment. Crit Rev Toxicol 1994, 24:87-149.
• [2]Evans MS, Noguchi GE, Rice CP: The biomagnifications of polychlorinated biphenyls, toxaphene, and DDT compounds in a Lake Michigan offshore food web. Arch Environ Contam Toxicol 1991, 20:87-93.
• [3]Kaiser K: On the optical activity of polychlorinated biphenyls. Environ Pollut 1974, 7:93-101.
• [4]Frame GM, Wagner RE, Carnahan JC, Brown JF Jr, May RJ, Smullen LA, Bedard DL: Comprehensive, quantitative congener-specific analyses of eight Aroclors and complete PCB congener assignments on DB-1 capillary GC columns. Chemosphere 1996, 33(4):603-623.
• [5]Robson M, Harrad S: Chiral PCB signatures in air and soil: Implications for atmospheric source apportionment. Environ Sci Technol 2004, 38:1662-1666.
• [6]Wong F, Robson M, Diamond M, Harrad S, Truong J: Concentrations and chiral signatures of POPs in soil and sediments: a comparative urban versus rural study in Canada and UK. Chemosphere 2009, 74:404-411.
• [7]Wong CS, Garrison AW, Foreman WT: Enantiomeric composition of chiral polychlorinated biphenyl atropisomers in aquatic bed sediment. Environ Sci Technol 2001, 35:33-39.
• [8]Wong CS, Garrison AW, Smith PD, Foreman WT: Enantiomeric composition of chiral polychlorinated biphenyl atropisomers in aquatic and riparian biota. Environ Sci Technol 2001, 35:2448-2454.
• [9]Ross MS, Verreault J, Letcher RJ, Gabrielsen GW, Wong CS: Chiral organochlorine contaminants in blood and eggs of glaucous gulls (Larus hyperboreus) from the Norwegian Arctic. Environ Sci Technol 2008, 42:7181-7186.
• [10]Serrano R, Fernandez M, Rabanal R, Hernandez LM, Gonzalez MJ: Congener-specific determination of polychlorinated biphenyls in shark and grouper livers from the Northwest African Atlantic Ocean. Arch Environ Contam Toxicol 2000, 38:217-224.
• [11]Reich S, Jimenez B, Marsili L, Hernández LM, Schurig V, González MJ: Congener specific determination and enantiomeric ratios of chiral polychlorinated biphenyls in striped dolphins (Stenella coeruleoalba) from the Mediterranean Sea. Environ Sci Technol 1999, 33:1787-1793.
• [12]Hoekstra PF, Wong CS, O’Hara TM, Solomon KR, Mabury SA, Muir DCG: Enantiomer-specific accumulation of PCB atropisomers in the bowhead whale (Balaena mysticetus). Environ Sci Technol 2002, 36:1419-1425.
• [13]Harrad S, Ren J, Hazrati S, Robson M: Chiral signatures of PCB#s 95 and 149 in indoor air, grass, duplicate diets and human faeces. Chemosphere 2006, 63:1368-1376.
• [14]Chu S, Covaci A, Schepens P: Levels and chiral signatures of persistent organochlorine pollutants in human tissues from Belgium. Environ Res 2003, 93:167-176.
• [15]Lehmler H-J, Harrad SJ, Hunerfuss H, Kania-Korwel I, Lee CM, Lu Z, Wong CS: Chiral polychlorinated biphenyl transport, metabolism, and distribution: a review. Environ Sci Technol 2010, 44:2757-2766.
• [16]Nezel T, Muller-Plathe F, Muller MD, Buser H-R: Theoretical considerations about chiral PCBs and their methylthio and methylsulfonyl metabolites being possibly present as stable enantiomers. Chemosphere 1997, 35:1895-1906.
• [17]Park J, Linderholm L, Charles MJ, Athanasiadou M, Petrik J, Kocan A, Drobna B, Trnovec T, Bergman A, Hertz-Picciotto I: Polychlorinated biphenyls and their hydroxylated metabolites (OH-PCBs) in pregnant women from eastern Slovakia. Environ Health Perspect 2007, 115:20-27.
• [18]Bergman A, Klasson-Wehler E, Kuroki H: Selective retention of hydroxylated PCB metabolites in blood. Environ Health Perspect 1994, 102:464-469.
• [19]Preston BD, Allen JR: 2,2′,5,5′-tetrachlorobiphenyl: isolation and identification of metaboliltes generated by rat liver microsomes. Drug Metabol Dispos 1980, 4:197-204.
• [20]Rezek J, Macek T, Mackova M, Triska J: Plant metabolites of polychlorinated biphenyls in hairy root culture of black nightshade Solanum nigrum SNC-9O. Chemosphere 2007, 69:1221-1227.
• [21]Fangstrom B, Athanasiadou M, Grandjean P, Weihe P, Bergman A: Hydroxylated PCB metabolites and PCBs in serum from pregnant faroese women. Environ Health Perspect 2002, 110:895-899.
• [22]Hovander L, Malmberg T, Athanasiadou M, Athanassiadis I, Rahm S, Bergman A, Wehler EK: Identification of hydroxylated PCB metabolites and other phenolic pollutants in halogenated human blood plasma. Arch Environ Contam Toxicol 2002, 42:105-117.
• [23]Fujihiro S, Higuchi R, Hisamatsu S, Sonoki S: Metabolism of hydroxylated PCB congeners by cloned laccase isoforms. Appl Microbiol Biotechnol 2009, 82:853-860.
• [24]Kania-Korwel I, Vyas SM, Song Y, Lehmler H-J: Gas chromatographic separation of methoxylated polychlorinated biphenyl atropisomers. J Chromatogr A 2008, 1207:146-154.
• [25]Kania-Korwel I, Zhao H, Norstrom K, Li X, Hornbuckle KC, Lehmler H-J: Simultaneous extraction and clean-up of PCBs and their metabolites from small tissue samples using pressurized liquid extraction. J Chromatogr A 2008, 1214:37-46.
• [26]Abraham VM, Lynn BC Jr: Determination of hydroxylated polychlorinated biphenyls by ion trap gas chromatography–tandem mass spectrometry. J Chromatogr A 1997, 790:131-141.
• [27]Sandanger TM, Dumas P, Berger U, Burkow IC: Analysis of HO-PCBs and PCP in blood plasma from individuals with high PCB exposure living on the Chukotka Peninsula in the Russian Arctic. J Environ Monit 2004, 6:758-765.
• [28]Sandau CD, Ayotte P, Dewailly E, Duffe J, Norstrom RJ: Analysis of hydroxylated metabolites of PCBs (OH-PCBs) and other chlorinated phenolic compounds in whole blood from Canadian Inuit. Environ Health Perspect 2000, 108:611-616.
• [29]Letcher RJ, Li HX, Chu SG: Determination of hydroxylated polychlorinated biphenyls (HO-PCBs) in blood plasma by high-performance liquid chromatography-electrospray ionization-tandem quadrupole mass spectrometry. J Anal Toxicol 2005, 29:209-216.
• [30]Kania-Korwel I, Barnhart CD, Stamou M, Truong KM, El-Komy MHME, Lein PJ, Veng-Pedersen P, Lehmler H-J: 2,2′,3,5′,6-Pentachlorobiphenyl (PCB 95) and its hydroxylated metabolites are enantiomerically enriched in female mice. Environ Sci Technol 2012, 46:11393-11401.
• [31]Kania-Korwel I, Duffel MW, Lehmler H-J: Gas chromatographic analysis with chiral cyclodextrin phases reveals the enantioselective formation of hydroxylated polychlorinated biphenyls by rat liver microsomes. Environ Sci Technol 2011, 45:9590-9596.
• [32]Wu X, Pramanik A, Duffel MW, Hrycay EG, Bandiera SM, Lehmler H-J, Kania-Korwel I: 2,2′,3,3′,6,6′-Hexachlorobiphenyl (PCB136) Is enantioselectively oxidized to hydroxylated metabolites by rat liver microsomes. Chem Res Toxicol 2011, 24:2249-2257.
• [33]Pham-Tuan H, Larsson C, Hoffmann F, Bergman A, Fröba M, Hühnerfuss H: Enantioselective semipreparative HPLC separation of PCB metabolites and their absolute structure elucidation using electronic and vibrational circular dichroism. Chirality 2005, 17:266-280.
• [34]Kunisue T, Tanabe S: Hydroxylated polychlorinated biphenyls (OH-PCBs) in the blood of mammals and birds from Japan: Lower chlorinated OH-PCBs and profiles. Chemosphere 2009, 74:950-961.
• [35]Lehmler HJ, Robertson LW: Synthesis of hydroxylated PCB metabolites with the Suzuki-coupling. Chemosphere 2001, 45:1119-1127.
• [36]Bauer U, Amaro AR, Robertson LW: A new strategy for the synthesis of polychlorinated biphenyl metabolites. Chem Res Toxicol 1995, 8:92-95.
• [37]Determination of LODs (limits of detection) and LOQs (limit of quantification) http://www.und.edu/dept/chromatography/Docs/Determination%20of%20LODs.pdf webcite