Analytical and Bioanalytical Chemistry

, Volume 403, Issue 6, pp 1501–1522 | Cite as

Hyphenated techniques as tools for speciation analysis of metal-based pharmaceuticals: developments and applications

  • Björn Meermann
  • Michael Sperling


Method development and applications of hyphenated techniques as tools for speciation analysis of metal-based pharmaceuticals are summarized within this review. Advantages and limitations of the separation modes—high-performance liquid chromatography (HPLC), capillary electrophoresis (CE), and gas chromatography (GC)—as well as the detection modes—inductively coupled plasma–mass spectrometry (ICP-MS) and electrospray ionization–mass spectrometry (ESI-MS)—are discussed. ICP-MS detection is found to be advantageous for the quantification of drugs containing metals and other heteroatoms. The species-independent sensitivity and multielement capabilities of ICP-MS allow it to be used for quantification even when species-specific standards are not available, as well as to determine the stoichiometry in metallodrug–biomolecule interactions. Molecular information that is totally destroyed when ICP is applied as ionization source and is therefore not obtainable via ICP-MS detection can be accessed by the complementary technique of ESI-MS. Speciation analysis combining both elemental and molecular information is therefore a powerful tool for the analysis of metal-based pharmaceuticals and their metabolites in body fluids and other relevant matrices.


Method development and applications of hyphenated techniques as tools for speciation analysis of metal-based pharmaceuticals are summarized within this review. Advantages and limitations of both the separation modules and the detection modules mainly such as inductively coupled plasma- (ICP-MS) or electrospray ionization-mass spectrometry (ESIMS) are discussed. ICP-MS detection is found to be advantageous for the quantification of drugs containing metals other heteroatoms while molecular information totally destroyed by the plasma and therefore not obtainable by means of ICP-MS detection is the domain of the complementary used ESI-MS.


Speciation analysis Hyphenated techniques Metal-based pharmaceuticals Metallodrugs Complementary information ICP-MS ESI-MS 





Atomic absorption spectroscopy


Atomic fluorescence spectroscopy


Adenosine monophosphate


Acute promyelocytic leukemia


Arsenic trioxide






Capillary electrophoresis


Diethylenetriaminepentaacetic acid (copper complex)


Deoxyribonucleic acid


Dynamic reaction cell


Electron capture dissociation


Electroosmotic flow


Electrospray ionization–mass spectrometry


Diethylenetriaminepentaacetic acid (iron complex)


Gas chromatography


Gadobenate dimeglumine (Multihance)


Gadobutrol (Gadovist)


Gadoteric acid (Dotarem)


Gadopentetate dimeglumine (Magnevist)


Gadodiamide (Omniscan)


Guanosine monophosphate






Hydrophilic interaction chromatography


Human immunodeficiency virus


High resolution


High-temperature liquid chromatography


Ion chromatography


Inductively coupled plasma–atomic emission spectroscopy


Inductively coupled plasma–mass spectrometry


Inductively coupled plasma–optical emission spectrometry


International Union of Pure and Applied Chemistry


Indazolium [bis-indazoletetrachlororuthenate(III)]


Sodium [bis-indazoletetrachlororuthenate(III)]


Limit of detection


Limit of quantification


Motexafin gadolinium


Motexafin lutetium


Magnetic resonance imaging


Imidazolium [trans-imidazolemethylsulfoxidetetrachlororuthenate(III)]


Nephrogenic systemic fibrosis


(Reverse-phase) high-performance liquid chromatography


Size-exclusion chromatography


Solid-phase extraction


Synchrotron radiation-induced X-ray emission


Thin-layer chromatography


Ultraviolet/visible (spectroscopy)




Diethylenetriaminepentaacetic acid (zinc complex)



Prof. Dr. U. Karst is acknowledged for supporting this work.


  1. 1.
    Templeton DM, Ariese F, Cornelis R, Danielsson R-G, Muntau H, Van Leeuwen HP, Lobinski R (2000) Pure Appl Chem 72:1453–1470CrossRefGoogle Scholar
  2. 2.
    Sanz-Medel A, Montes-Bayón M, Fernández Sánchez ML (2003) Anal Bioanal Chem 377:236–247CrossRefGoogle Scholar
  3. 3.
    Fricker PS (2007) Dalton Trans 43:4903–4917CrossRefGoogle Scholar
  4. 4.
    Brouwers EEM, Tibben M, Rosing H, Schellens JHM, Beijnen JH (2008) Mass Spectrom Rev 27:67–100CrossRefGoogle Scholar
  5. 5.
    Hann S, Koellensperger G, Zs S, Stingeder G, Fürhacker M, Buchberger W, Mader RM (2003) J Anal At Spectrom 18:1391–1395CrossRefGoogle Scholar
  6. 6.
    Galettis P, Carr JL, Paxton JW, McKeage MJ (1999) J Anal At Spectrom 14:953–956CrossRefGoogle Scholar
  7. 7.
    Trümpler S, Lohmann W, Meermann B, Buscher W, Sperling M, Karst U (2009) Metallomics 1:87–91CrossRefGoogle Scholar
  8. 8.
    Sulyok M, Hann S, Hartinger CG, Keppler BK, Stingeder G, Koellensperger G (2005) J Anal At Spectrom 20:856–863CrossRefGoogle Scholar
  9. 9.
    Szpunar J, Makarov A, Pieper T, Keppler BK, Lobinski R (1999) Anal Chim Acta 387:135–144CrossRefGoogle Scholar
  10. 10.
    Künnemeyer J, Terborg L, Nowak S, Scheffer A, Telgmann L, Tokmak F, Günsel A, Wiesmüller A, Reichelt S, Karst U (2008) Anal Chem 80:8163–8170CrossRefGoogle Scholar
  11. 11.
    Künnemeyer J, Terborg L, Meermann B, Brauckmann C, Möller I, Scheffer A, Karst U (2009) Environ Sci Technol 43:2884–2890CrossRefGoogle Scholar
  12. 12.
    Wuilloud RG, Selar N, Kannamkumarath SS, Caruso JA (2004) J Anal At Spectrom 19:1442–1447CrossRefGoogle Scholar
  13. 13.
    Miekeley N, Mortari SR, Schubach AO (2002) Anal Bioanal Chem 372:495–502CrossRefGoogle Scholar
  14. 14.
    Jahn MR, Mrestani Y, Langguth P, Neubert RHH (2007) Electrophoresis 28:2424–2429CrossRefGoogle Scholar
  15. 15.
    Montes-Bayon M, Pröfrock D, Sanz-Medel A, Prange A (2006) J Chromatogr A 1114:138–144CrossRefGoogle Scholar
  16. 16.
    Gibičar D, Logar M, Horvat N, Marn-Pernat A, Ponikvar R, Horvat M (2007) Anal Bioanal Chem 388:329–340CrossRefGoogle Scholar
  17. 17.
    O’Brien TP, Dowling TM, Moeder CW, Bicker GR (1999) J Pharm Biomed Anal 25:327–333CrossRefGoogle Scholar
  18. 18.
    Rao RN, Talluri MVNK (2007) J Pharm Biomed Anal 43:1–13CrossRefGoogle Scholar
  19. 19.
    Wilson ID, Brinkman UATh (2003) J Chromatogr A 1000:325–356CrossRefGoogle Scholar
  20. 20.
    Wilson ID, Brinkman UATh (2007) Trends Anal Chem 26:847–854CrossRefGoogle Scholar
  21. 21.
    Corcoran O, Nicholson JK, Lenz EM, Abou-Shakra F, Castro-Perez J, Sage AB, Wilson ID (2000) Rapid Commun Mass Spectrom 14:2377–2384CrossRefGoogle Scholar
  22. 22.
    Nygren Y, Björn E (2010) J Chromatogr A 1217:4980–4986CrossRefGoogle Scholar
  23. 23.
    Michalke B (2002) Trends Anal Chem 21:154–165CrossRefGoogle Scholar
  24. 24.
    Gammelgaard B, Hansen HR, Stürup S, Moller C (2008) Expert Opin Drug Metab Toxicol 4:1187–1207CrossRefGoogle Scholar
  25. 25.
    Smith C, Jensen BP, Wilson ID, Abou-Shakra F, Crowther D (2004) Rapid Commun Mass Spectrom 18:1487–1492CrossRefGoogle Scholar
  26. 26.
    Rivas C, Ebdon L, Hill SJ (1996) J Anal At Spectrom 11:1147–1150CrossRefGoogle Scholar
  27. 27.
    Chassaigne H, Lobinski R (1998) Fresenius’ J Anal Chem 361:267–273Google Scholar
  28. 28.
    Rottmann L, Heumann KG (1994) Fresenius’ J Anal Chem 350:221–227Google Scholar
  29. 29.
    Bluemlein K, Krupp EM, Feldmann J (2009) J Anal At Spectrom 24:108–113CrossRefGoogle Scholar
  30. 30.
    Pröfrock D, Prange A (2009) J Chromatogr A 1216:6706–6715CrossRefGoogle Scholar
  31. 31.
    Meermann B, Kießhauer M (2011) J Anal At Spectrom 26:2069–2075CrossRefGoogle Scholar
  32. 32.
    Vlieger JSB, Giezen MJN, Falck D, Tump C, van Heuveln F, Giera M, Kool J, Lingeman H, Wieling J, Honing M, Irth H, Niessen WMA (2011) Anal Chim Acta 698:69–76CrossRefGoogle Scholar
  33. 33.
    Vanhaecke F (2002) Anal Bioanal Chem 372:20–21CrossRefGoogle Scholar
  34. 34.
    Jackson GP, King FL, Duckworth DC (2003) J Anal At Spectrom 18:1026–1032CrossRefGoogle Scholar
  35. 35.
    Lokits KE, Limbach PA, Caruso JA (2009) J Anal At Spectrom 24:528–534CrossRefGoogle Scholar
  36. 36.
    Giusti P, Schaumlöffel D, Encinar JR, Szpunar J (2005) J Anal At Spectrom 20:1101–1107CrossRefGoogle Scholar
  37. 37.
    Sakurai H (2010) J Health Sci 56:129–143CrossRefGoogle Scholar
  38. 38.
    Rosenberg B, VanCamp L, Trosko JE, Mansour VH (1969) Nature 222:385–386CrossRefGoogle Scholar
  39. 39.
    García Sar D, Montes-Bayón M, Blanco González E, Sierra Zapico LM, Sanz-Medel A (2011) Chem Res Toxicol 24:896–904CrossRefGoogle Scholar
  40. 40.
    Wheate NJ, Walker S, Craig GE, Oun R (2010) Dalton Trans 39:8113–8127CrossRefGoogle Scholar
  41. 41.
    Graf N, Ang WH, Zhu G, Myint MNZ, Lippard SJ (2011) Chem Bio Chem 12:1115–1123Google Scholar
  42. 42.
    Guainazzi A, Schärer OD (2010) Cell Mol Life Sci 67:3683–3697CrossRefGoogle Scholar
  43. 43.
    Ceresa C, Cavaletti G (2011) Curr Med Chem 18:329–341Google Scholar
  44. 44.
    Esteban-Fernández D, Cañas B, Pizarro I, Palacios A, Gómez-Gómez MM (2007) J Anal At Spectrom 22:1113–1121CrossRefGoogle Scholar
  45. 45.
    Michalke B (2010) J Trace Elem Med Biol 24:69–77CrossRefGoogle Scholar
  46. 46.
    Vacchina V, Torti L, Allievi C, Lobinski R (2003) J Anal At Spectrom 18:884–890CrossRefGoogle Scholar
  47. 47.
    Bell DN, Liu JJ, Tingle MD, McKeage MJ (2006) J Chromatogr B 837:29–34CrossRefGoogle Scholar
  48. 48.
    Falta T, Koellensperger G, Standler A, Buchberger W, Mader RM, Hann S (2009) J Anal At Spectrom 24:1336–1342CrossRefGoogle Scholar
  49. 49.
    Smith CJ, Wilson ID, Abou-Shakra F, Payne R, Grisedale H, Long A, Roberts D, Malone M (2002) Chromatographia 55:S151–S155CrossRefGoogle Scholar
  50. 50.
    Hann S, Zs S, Lenz K, Stingeder G (2005) Anal Bioanal Chem 381:405–412CrossRefGoogle Scholar
  51. 51.
    Khuhawar MY, Arain GM (2005) Talanta 66:34–39CrossRefGoogle Scholar
  52. 52.
    Lenz K, Hann S, Koellensperger G, Stefanka Z, Stingeder G, Weissenbacher N, Mahnik SN, Fuerhacker M (2005) Sci Total Environ 345:141–152CrossRefGoogle Scholar
  53. 53.
    Lenz K, Koellensperger G, Hann S, Weissenbacher N, Mahnik SN, Fuerhacker M (2007) Chemosphere 69:1765–1774CrossRefGoogle Scholar
  54. 54.
    Hall MD, Dillon CT, Zhang M, Beale P, Cai Z, Lai B, Stampfl APJ, Hambley TW (2003) J Biol Inorg Chem 8:726–732CrossRefGoogle Scholar
  55. 55.
    Smit T, Snyman JR, Neuse EW, Bohm L, van Rensburg CE (2005) Anti Cancer Drugs 16:501–506CrossRefGoogle Scholar
  56. 56.
    Esteban-Fernández D, Gómez-Gómez MM, Cañas B, Verdaguer JM, Ramírez R, Palacios MA (2007) Talanta 72:768–773CrossRefGoogle Scholar
  57. 57.
    Moreno-Gordaliza E, Canas B, Palacios MA, Gómez-Gómez MM (2010) Analyst 135:1288–1298CrossRefGoogle Scholar
  58. 58.
    Zhao Z, Tepperman K, Dorsey JG, Elder RC (1993) J Chromatogr 615:83–89CrossRefGoogle Scholar
  59. 59.
    Heudi O, Cailleux A, Allain P (1998) J Inorg Biochem 71:61–69CrossRefGoogle Scholar
  60. 60.
    Allain P, Heudi O, Cailleux A, Le Bouil A, Larra F, Boisdron-Celle M, Gamelin E (2000) Drug Metab Dispos 28:1379–1384Google Scholar
  61. 61.
    Stefánka Zs, Hann S, Koellensperger G, Stingeder G (2004) J Anal At Spectrom 19:894–898CrossRefGoogle Scholar
  62. 62.
    Timerbaev AR, Aleksenko SS, Polec-Pwlak K, Ruzik R, Semenova O, Hartinger CG, Oszwaldowski S, Galanski M, Jarosz M, Keppler BK (2004) Electrophoresis 25:1988–1995CrossRefGoogle Scholar
  63. 63.
    Xie RM, Johnson W, Rodriguez L, Gounder M, Hall GS, Buckley B (2007) Anal Bioanal Chem 387:2815–2822CrossRefGoogle Scholar
  64. 64.
    Mandal R, Kalke R, Li X-F (2003) Rapid Commun Mass Spectrom 17:2748–2754CrossRefGoogle Scholar
  65. 65.
    Mandal R, Kalke R, Li X-F (2004) Chem Res Toxicol 17:1391–1397CrossRefGoogle Scholar
  66. 66.
    Mandal R, Sawyer MB, Li X-F (2006) Rapid Commun Mass Spectrom 20:2533–2538CrossRefGoogle Scholar
  67. 67.
    Zayed A, Jones GDD, Reid HJ, Shoeib T, Taylor SE, Thomas AL, Wood JP, Sharp BL (2011) Metallomics 3:991–1000CrossRefGoogle Scholar
  68. 68.
    Harrington CF, Le Pla RC, Jones GDD, Thomas AL, Farmer PB (2010) Chem Res Toxicol 23:1313–1321CrossRefGoogle Scholar
  69. 69.
    Desoize B, Madoulet C (2002) Crit Rev Oncol Hemat 42:317–325CrossRefGoogle Scholar
  70. 70.
    Alessio E, Mestroni G, Bergamo A, Sava G (2004) Curr Top Med Chem 4:1525–1535CrossRefGoogle Scholar
  71. 71.
    Timerbaev AR, Pawlak K, Gabbiani C, Messori L (2011) Trends Anal Chem 30:1123CrossRefGoogle Scholar
  72. 72.
    Bouma M, Nuijen B, Jansen MT, Sava G, Picotti F, Flaibani A, Bult A, Beijnen JH (2003) J Pharm Biomed Anal 31:215–228CrossRefGoogle Scholar
  73. 73.
    Heffeter P, Böck K, Atil B, Reza Hoda MA, Körner W, Bartel C, Jungwirth U, Keppler BK, Micksche M, Berger W, Koellensperger G (2010) J Biol Chem 15:737–748Google Scholar
  74. 74.
    Timerbaev AR, Rudnev AV, Semenova O, Hartinger CG, Keppler BK (2005) Anal Biochem 341:326–333CrossRefGoogle Scholar
  75. 75.
    Polec-Pawlac K, Abramski JK, Semenova O, Hartinger CG, Timerbaev AR, Keppler BK, Jarosz M (2006) Electrophoresis 27:1128–1135CrossRefGoogle Scholar
  76. 76.
    Timerbaev AR, Foteeva LS, Rudnev AV, Abramski JK, Polec-Pawlak K, Hartinger CG, Jarosz M, Keppler BK (2007) Electrophoresis 28:2235–2240CrossRefGoogle Scholar
  77. 77.
    Bytzek AK, Boeck K, Hermann G, Hann S, Keppler BK, Hartinger CG, Koellensperger G (2011) Metallomics 3:1049–1055CrossRefGoogle Scholar
  78. 78.
    Küng A, Pieper T, Keppler BK (2001) J Chromatogr B 759:81–89CrossRefGoogle Scholar
  79. 79.
    Olszewski U, Claffey J, Hogan M, Tacke M, Zeillinger R, Bednarski PJ, Hamilton G (2011) Invest New Drugs 29:607–614CrossRefGoogle Scholar
  80. 80.
    Meléndez E (2002) Crit Rev Oncol Hemat 42:309–315CrossRefGoogle Scholar
  81. 81.
    Vera JL, Román FR, Meléndez E (2004) Anal Bioanal Chem 379:399–403CrossRefGoogle Scholar
  82. 82.
    Sarsam SW, Nutt DR, Strohfeldt K, Watson KA (2011) Metallomics 3:152–161CrossRefGoogle Scholar
  83. 83.
    Fujisawa S, Ohno R, Shigeno K, Sahara N, Nakamura S, Naito K, Kobayashi M, Shinjo K, Takeshita A, Suzuki Y, Hashimoto H, Kinoshita K, Shimoya M, Kaise T, Ohnishi K (2007) Cancer Chemother Pharmacol 59:485–493CrossRefGoogle Scholar
  84. 84.
    McNeely SC, Belshoff AC, Taylor BF, Fan TW-M, McCabe MJ Jr, Pinhas AR, States JC (2008) Toxicol Appl Pharmacol 229:252–261CrossRefGoogle Scholar
  85. 85.
    Fukai Y, Hirata M, Ueno M, Ichikawa N, Kobayashi H, Saitoh H, Sukurai T, Kinoshita K, Kaise T, Ohta S (2006) Biol Pharm Bull 29:1022–1027CrossRefGoogle Scholar
  86. 86.
    Wang ZW, Zhou J, Lu X, Gong Z, Le XC (2004) Chem Res Toxicol 17:95–103CrossRefGoogle Scholar
  87. 87.
    Kiguchi T, Yoshino Y, Yuan B, Yoshizawa S, Kitahara T, Akahane D, Gotoh M, Kaise T, Toyoda H, Ohyashiki K (2010) Leukemia Res 34:403–405CrossRefGoogle Scholar
  88. 88.
    Bohrer D, do Nascimento PC, Becker E, de Carvalho LM, Dessuy M (2005) J Parent Enteral Nutr 29:1–7CrossRefGoogle Scholar
  89. 89.
    de Moraes FEM, dos Santos EP, Barin JS, Zanella R, Dressler VL, Bittencourt CF (2002) J Anal At Spectrom 17:819–823CrossRefGoogle Scholar
  90. 90.
    Pal A, Gupta S, Jaiswal A, Dube A, Vyas SP (2012) J Liposome Res 22:62–71CrossRefGoogle Scholar
  91. 91.
    Chappuis F, Sundar S, Hailu A, Ghalib H, Rijal S, Peeling RW, Alvar J, Boelaert M (2007) Nat Rev Microbiol 5:873–882CrossRefGoogle Scholar
  92. 92.
    Frézard F, Demicheli C (2010) Expert Opin Drug Deliv 7:1343–1358CrossRefGoogle Scholar
  93. 93.
    de Figueiredo EC, Luccas PO, Arruda MAZ (2006) Anal Lett 39:543–554CrossRefGoogle Scholar
  94. 94.
    Almeida VGK, Lima MF, Cassella RJ (2007) Talanta 71:1047–1053CrossRefGoogle Scholar
  95. 95.
    de Moraes FEM, Paula FR, da Silva FEB, de Moraes DP, Paniz JNG, dos Santos EP, Dressler VL, Bittencourt CF (2003) At Spectrosc 24:15–21Google Scholar
  96. 96.
    Lukaszczyk L, Zyrnicki W (2010) J Pharm Biomed Anal 52:747–751CrossRefGoogle Scholar
  97. 97.
    Shaked-Mishan P, Ulrich N, Ephros M, Zilberstein D (2001) Biol Chem 276:3971–3976CrossRefGoogle Scholar
  98. 98.
    Lee MB, Gilbert HM (1999) Infect Med 16:37–45Google Scholar
  99. 99.
    Ge R, Sun H (2007) Acc Chem Res 40:267–274CrossRefGoogle Scholar
  100. 100.
    Li Y, Liu J-M, Han F, Jiang Y, Yan X-P (2011) J Anal At Spectrom 26:94–99CrossRefGoogle Scholar
  101. 101.
    Sundar S, Chakravarty J (2010) Int J Environ Res Public Health 7:4267–4277CrossRefGoogle Scholar
  102. 102.
    Fricker SP (1996) Transition Met Chem 21:377–383CrossRefGoogle Scholar
  103. 103.
    Heath M (1988) J Ann Rheum Dis 47:18–21CrossRefGoogle Scholar
  104. 104.
    Berners-Price SJ, Filipovska A (2011) Metallomics 3:863–873CrossRefGoogle Scholar
  105. 105.
    Tiekink ERT (2002) Crit Rev Oncol Hemat 42:225–248CrossRefGoogle Scholar
  106. 106.
    Fonteh P, Meyer D (2009) Metallomics 1:427–433CrossRefGoogle Scholar
  107. 107.
    Fonteh PN, Keter FK, Meyer D (2010) Biometals 23:185–196CrossRefGoogle Scholar
  108. 108.
    Lewis MG, DaFonseca S, Chomont N, Palamara AT, Tardugno M, Mai A, Collins M, Wagner WL, Yalley-Ogunro J, Greenhouse J, Chirullo B, Norelli S, Garaci E, Savarino A (2011) AIDS 25:1347–1356CrossRefGoogle Scholar
  109. 109.
    Ghanizadeh A (2011) Toxicology 283:63–64CrossRefGoogle Scholar
  110. 110.
    Sakurai H, Katoh A, Kiss T, Jakusch T, Hattori M (2010) Metallomics 2:670–682CrossRefGoogle Scholar
  111. 111.
    Karmaker S, Saha TK, Yoshikawa Y, Sakurai H (2010) Afr J Pharm Pharmacol 4:235–243Google Scholar
  112. 112.
    Islam Md N, Kumbhar AA, Kumbhar AS, Zeller M, Butcher RJ, Dusane MB, Joshi BN (2010) Inorg Chem 49:8237–8246CrossRefGoogle Scholar
  113. 113.
    Passadouro M, Metelo AM, Melao AS, Pedro JR, Faneca H, Carvalho E, Margarida M, Castro CA (2010) J Inorg Biochem 104:987–992CrossRefGoogle Scholar
  114. 114.
    Walmsley RS, Tshentu ZR, Fernandes MA, Frost CL (2010) Inorg Chim Acta 363:2215–2221CrossRefGoogle Scholar
  115. 115.
    Chéry CC, De Cremer K, Cornelis R, Vanhaecke F, Moens L (2003) J Anal At Spectrom 18:1113–1118CrossRefGoogle Scholar
  116. 116.
    Gómez-Gómez MM, Rodríguez-Farinas N, Canas-Montalvo B, Domínguez J, Guinovart J, Cámara-Rica C (2011) Talanta 84:1011–1018CrossRefGoogle Scholar
  117. 117.
    Rodríguez-Fariñas N, Gomez-Gomez MM, Camara-Rica C (2008) Anal Bioanal Chem 390:29–35CrossRefGoogle Scholar
  118. 118.
    Thompson KH, Lichter J, LeBel C, Scaife MC, McNeill JH, Orvig C (2009) J Inorg Biochem 103:554–558CrossRefGoogle Scholar
  119. 119.
    Gammelgaard B, Jensen BP (2007) J Anal At Spectrom 22:235–249CrossRefGoogle Scholar
  120. 120.
    Carr JE, Dill AE, Kwok K, Carnahan JW, Webster GK (2008) Curr Pharma Anal 4:206–214CrossRefGoogle Scholar
  121. 121.
    Duckett CJ, Bailey NJC, Walker H, Abou-Shakra F, Wilson ID, Lindon JC, Nicholson JK (2002) Rapid Commun Mass Spectrom 16:245–247CrossRefGoogle Scholar
  122. 122.
    MacDonald C, Smith C, Michopoulos F, Weaver R, Wilson ID (2011) Rapid Commun Mass Spectrom 25:1787–1793CrossRefGoogle Scholar
  123. 123.
    De Wolf K, Balcaen LIL, Van De Walle E, Cuyckens F, Vanhaecke F (2010) J Anal At Spectrom 25:419–425CrossRefGoogle Scholar
  124. 124.
    Meermann B, Bockx M, Laenen A, Van Looveren C, Cuyckens F, Vanhaecke F (2012) Anal Bioanal Chem 402:439–448CrossRefGoogle Scholar
  125. 125.
    Cuyckens F, Balcaen LIL, De Wolf K, De Samber B, Van Looveren C, Hurkmans R, Vanhaecke F (2008) Anal Bioanal Chem 390:1717–1729CrossRefGoogle Scholar
  126. 126.
    Meermann B, Hulstaert A, Laenen A, Van Looveren C, Vliegen M, Cuyckens F, Vanhaecke F (2012) Anal Chem 84:2395–2401Google Scholar
  127. 127.
    Balcaen LIL, De Samber B, De Wolf K, Cuyckens F, Vanhaecke F (2007) Anal Bioanal Chem 389:777–786CrossRefGoogle Scholar
  128. 128.
    Jensen BP, Gammelgaard B, Hansen SH, Andersen JV (2005) J Anal At Spectrom 20:204–209CrossRefGoogle Scholar
  129. 129.
    Michalke B, Schramel P, Witte H (2000) Biol Trace Elem Res 78:81–91CrossRefGoogle Scholar
  130. 130.
    Michalke B, Schramel P, Witte H (2000) Biol Trace Elem Res 78:67–79CrossRefGoogle Scholar
  131. 131.
    Kannamkumarath SS, Wuilloud RG, Stalcup A, Caruso JA, Patel H, Sakr A (2004) J Anal At Spectrom 19:107–113CrossRefGoogle Scholar
  132. 132.
    Meermann B, Möller I, Nowak S, Luftmann H, Karst U (2010) J Anal At Spectrom 25:1654–1658CrossRefGoogle Scholar
  133. 133.
    Seitz W, Weber WH, Flottmann D, Schulz W (2004) Chem Lab Biotechn 12:456–460Google Scholar
  134. 134.
    Sacher F, Raue B, Brauch H-J (2005) J Chromatogr A 1085:117–123CrossRefGoogle Scholar
  135. 135.
    Künnemeyer J, Terborg L, Nowak S, Brauckmann C, Telgmann L, Albert A, Tokmak F, Krämer BK, Günsel A, Wiesmüller GA, Karst U (2009) Electrophoresis 30:1766–1773CrossRefGoogle Scholar
  136. 136.
    Cleveland D, Long SE, Sander LC, Davis WC, Murphy KE, Case RJ, Rimmer CA, Francini L, Patri AK (2010) Anal Bioanal Chem 398:2987–2995CrossRefGoogle Scholar
  137. 137.
    Loreti V, Bettmer J (2004) Anal Bioanal Chem 379:1050–1054CrossRefGoogle Scholar
  138. 138.
    Künnemeyer J, Terborg L, Nowak S, Telgmann L, Tokmak F, Krämer BK, Günsel A, Wiesmüller GA, Waldeck J, Bremer C, Karst U (2009) Anal Chem 81:3600–3607CrossRefGoogle Scholar
  139. 139.
    Puttagunta NR, Gibby WA, Smith GT (1996) Invest Radiol 31:739–742CrossRefGoogle Scholar
  140. 140.
    Gibby WA, Gibby KA, Gibby WA (2004) Invest Radiol 39:138–142CrossRefGoogle Scholar
  141. 141.
    Kesava Raju CS, Cossmer A, Scharf H, Panne U, Lück D (2010) J Anal At Spectrom 25:55–61CrossRefGoogle Scholar
  142. 142.
    Parise RA, Miles DR, Egorin MJ (2000) J Chromatogr B 749:145–152CrossRefGoogle Scholar
  143. 143.
    Quirino JP, Dulay MT, Fu L, Mody TD, Zare RN (2002) J Sep Sci 25:819–824CrossRefGoogle Scholar
  144. 144.
    Geninatti-Crich S, Alberti D, Szabo I, Deagostino A, Toppino A, Barge A, Ballarini F, Bortolussi S, Bruschi P, Protti N, Stella S, Altieri S, Venturello P, Aime S (2011) Chem Eur J 17:8479–8486CrossRefGoogle Scholar
  145. 145.
    Miles DR, Mesfin M, Mody TD, Stiles M, Lee J, Fiene J, Denis B, Boswell GW (2006) Anal Bioanal Chem 385:345–356CrossRefGoogle Scholar
  146. 146.
    Rogers DA, Ray SJ, Hieftje GM (2010) Metallomics 2:271–279CrossRefGoogle Scholar
  147. 147.
    Luo X, Chen B, Ding L, Tang F, Yao S (2006) Anal Chim Acta 562:185–189CrossRefGoogle Scholar
  148. 148.
    Sutton KL, de Leon CAP, Ackley KL, Sutton RMC, Stalcup AM, Caruso JA (2000) Analyst 125:281–286CrossRefGoogle Scholar
  149. 149.
    Makarov A, Szpunar J (1999) J Anal At Spectrom 14:1323–1327CrossRefGoogle Scholar
  150. 150.
    Zhao Z, Jones WB, Teppermann K, Dorsey JG, Elder RC (1992) J Pharm Biomed Anal 10:279–287CrossRefGoogle Scholar
  151. 151.
    Lohmann W, Meermann B, Möller I, Scheffer A, Karst U (2008) Anal Chem 80:9769–9775CrossRefGoogle Scholar
  152. 152.
    Cairns WRL, Ebdon L, Hill S (1996) J Fresenius’ J Anal Chem 355:202–208Google Scholar
  153. 153.
    Cairns WRL, Ebdon L, Hill S (1994) J Anal Proc 31:295–297Google Scholar
  154. 154.
    Evans EH, Wolff J-C, Eckers C (2001) Anal Chem 73:4722–4728CrossRefGoogle Scholar
  155. 155.
    Gika HG, Theodoridou A, Michopoulos F, Theodoridis G, Diza E, Settas L, Nikolaidis P, Smith C, Wilson ID (2009) J Pharm Biomed Anal 49:579–586CrossRefGoogle Scholar
  156. 156.
    Chassaigne H, Lobinski R (1998) Anal Chim Acta 359:227–235CrossRefGoogle Scholar
  157. 157.
    Kahakachchi CL, Moore DA (2009) J Anal At Spectrom 24:1389–1396CrossRefGoogle Scholar
  158. 158.
    Wang WH, Chen ZL, Davey DE, Naidu R (2009) Microchim Acta 165:167–172CrossRefGoogle Scholar
  159. 159.
    Stefánka Zs, Koellensperger G, Stingeder G, Hann S (2006) J Anal At Spectrom 21:86–89CrossRefGoogle Scholar
  160. 160.
    Li H-B, Chen F, Jiang Y (2000) J Chromatogr A 891:243–247CrossRefGoogle Scholar
  161. 161.
    Li H-B, Chen F (2000) Fresenius’ J Anal Chem 368:836–838Google Scholar
  162. 162.
    Pereira AS, Schelfaut M, Lynen F, Sandra P (2008) J Chromatogr A 1185:78–84CrossRefGoogle Scholar
  163. 163.
    Vinas P, Campillo N, García LI, Córdoba MH (1996) Anal Chim Acta 318:319–325CrossRefGoogle Scholar
  164. 164.
    Moller C, Stürup S, Hansen HR, Gammelgaard B (2009) J Anal At Spectrom 24:1208–1212CrossRefGoogle Scholar
  165. 165.
    Bytzek AK, Reithofer MR, Galanski M, Groessl M, Keppler BK, Hartinger CG (2010) Electrophoresis 31:1144–1150CrossRefGoogle Scholar
  166. 166.
    Tian X-D, Zhuang Z-X, Chen B, Wang X-R (1999) At Spectrosc 20:127–133Google Scholar
  167. 167.
    Jung M-J, Yang D-H, Sung Y-K, Kim M-J, Kang S-J, Kwon D-Y, Kwon Y (2009) Microchim Acta 164:345–349CrossRefGoogle Scholar
  168. 168.
    Yang L-I, Gao L-R, Zhang D-Q (2003) Anal Sci 19:897–902CrossRefGoogle Scholar
  169. 169.
    He B, Jiang G-B, Zhang M, Xu X-B (2000) At Spectrosc 21:143–148Google Scholar
  170. 170.
    Cabral LM, Juliano VNM, Dias LRS, Dornelas CB, Rodrigues CR, Villardi M, Castro HC, dos Santos TC (2008) Mem Inst Oswaldo Cruz Rio de Janeiro 103:130–137CrossRefGoogle Scholar
  171. 171.
    Ensafi AA, Chamjangali MA, Mansour HR (2004) Anal Sci 20:645–650CrossRefGoogle Scholar
  172. 172.
    Themelis DG, Tzanavaras PD, Kika FS, Sofoniou MC (2001) Fresenius’ J Anal Chem 371:364–368Google Scholar
  173. 173.
    Trivelin LA, Rohwedder JJR, Rath S (2006) Talanta 68:1536–1543CrossRefGoogle Scholar
  174. 174.
    Matz SG, Elder RC, Teppermann K (1989) J Anal At Spectrom 4:767–771CrossRefGoogle Scholar
  175. 175.
    González MJG, Renedo OD, Martínez MJA (2006) Electroanalysis 18:1159–1166CrossRefGoogle Scholar
  176. 176.
    Li S-X, Zheng F-Y (2008) Planta Med 74:1302–1397CrossRefGoogle Scholar
  177. 177.
    D’Cruz OJ, Uckun FM (2001) Toxicol Appl Pharmacol 170:104–112CrossRefGoogle Scholar
  178. 178.
    Crul M, van den Bongard HJGD, Tibben BB, van Tellingen O, Sava G, Schellens JHM, Beijnen JH (2001) Fresenius’ J Anal Chem 369:442–445Google Scholar
  179. 179.
    Gaillard S, Kubiak C, Stolz C, Bonnemain B, Chassard D (2002) Invest Radiol 37:161–166CrossRefGoogle Scholar
  180. 180.
    Lásztity A, Kelkó-Lévai Á, Varga I, Zih-Perényi K, Bertalan É (2002) Microchem J 73:59–63CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  1. 1.Institute of Inorganic and Analytical ChemistryWestfälische Wilhelms-Universität MünsterMünsterGermany
  2. 2.European Virtual Institute for Speciation Analysis (EVISA)MünsterGermany

Personalised recommendations