Phthalates determination in pharmaceutical formulae used in parenteral nutrition by LC-ES-MS: importance in public health

Abstract

A method for determining a group of phthalate esters in pharmaceutical formulae used in parenteral nutrition samples (with and without vitamins) has been developed. The phthalic acid esters (PAEs) studied were dimethyl phthalate, diethyl phthalate, butyl benzyl phthalate, dibutyl phthalate, di-(2-ethylhexyl) phthalate, and dioctyl phthalate. This group of phthalates was determined by high performance liquid chromatography (HPLC)–electrospray ionization–mass spectrometry, working in positive ion mode. The phthalates analyzed were extracted from the sample using hexane and sodium hydroxide. The hexane was then evaporated, and the compounds were redissolved in acetonitrile. The compounds were separated by HPLC working in gradient mode with acetonitrile-ultrapure water starting from 5% to 75% acetonitrile in 5 min, followed by isocratic elution for 27 min. Standard calibration curves were linear for all the analytes over the concentration range 10–250 µg L−1. The method was precise (with RSD from 3.3% to 12.9%) and sensitive. The proposed analytical method has been applied to the analysis of these compounds in different pharmaceutical formulae (with different compositions) for parenteral nutrition samples in order to check the presence of phthalates and determine their concentration.

Parenteral nutrition sample stored in an ethyl vinyl acetate bag.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2

References

  1. 1.

    Communication from the Commission to the Council and The European Parliament on the implementation of the community strategy for endocrine disrupters-a range of substances suspected of interfering with the hormone system of humans and wildlife, COM (1999) 706; COM (2001) 262 final, Brussels, 2001

  2. 2.

    US Environmental Protection Agency (EPA) (1999) Protection agency. Introduction to water policy standards. Office of Water, Washington, DC

  3. 3.

    De OD, Gagliardi L, Porrá R, Berri S, Chimenti P, Granese A, Carpani I, Tonelli D (2006) Anal Chim Acta 555:238–241

    Article  Google Scholar 

  4. 4.

    Kato K, Shoda S, Takahashi M, Doi N, Yoshimura Y, Nakazawa H (2003) J Chromatogr B 788:407–411

    Article  CAS  Google Scholar 

  5. 5.

    Mortensen GK, MainK M, Anderson AM, Leffer H, Skakkeback NE (2005) Anal Bioanal Chem 382:1084–1092

    Article  CAS  Google Scholar 

  6. 6.

    Soresen LK (2006) Rapad Commu Mass Spectrom 20:1135–1143

    Article  Google Scholar 

  7. 7.

    Faouzi MA, Dine T, Gressier B, Kambia K, Luyckx M, Pagniez D, Brunet C, Cazin M, Babeles A, Cazin JC (1999) Inter J Pharma 180:113–121

    Article  CAS  Google Scholar 

  8. 8.

    Kambia K, Dine T, Gressier B, Germe AF, Luyckx M, Brunet C, Michaud L, Gottrand F (2001) J Chromatogr 755:297–303

    Article  CAS  Google Scholar 

  9. 9.

    Kambia K, Dine T, Gressier B, Germe AF, Luyckx M, Brunet C, Michaud L, Gottrand F (2003) Inter J Pharma 262:83–91

    Article  CAS  Google Scholar 

  10. 10.

    Ji-an C, Huijie L, Zhiqun Q, Weiqun S (2008) Environ Poll 156:849–853

    Article  Google Scholar 

  11. 11.

    Farahani H, Reza M, Dinarvand R, Norouzi P (2008) Talanta 76:718–723

    Article  CAS  Google Scholar 

  12. 12.

    Batlle R, Nerin C (2004) J Chromatogr A 1045:29–35

    Article  CAS  Google Scholar 

  13. 13.

    Silva MJ, Preau JL Jr, Needham LL, Calafat AM (2008) J Chromatogr B 873:180–186

    Article  CAS  Google Scholar 

  14. 14.

    Del Carlo M, Pepe A, Sacchetti G, Compagnone D, Mastrocola D, Cichelli A (2008) Food Chem 111:771–777

    Article  Google Scholar 

  15. 15.

    Zafra-Gómez A, Ballesteros O, Navalón A, Vilches JL (2008) Michrochem J 88:87–94

    Article  Google Scholar 

  16. 16.

    Kato K, Silva MJ, Needham LL, Calafat AM (2005) J Chromatogr B 814:355–360

    Article  CAS  Google Scholar 

  17. 17.

    Cai Ya-Qi, Jiang G-B, Liu Ping-Fu, Zhou P-X (2003) Anal Chim Acta 494:149–156

    Article  CAS  Google Scholar 

  18. 18.

    Luks-Betlej K, Popp P, Janozska B, Paschke H (2001) J Chromatogr A 938:93–101

    Article  CAS  Google Scholar 

  19. 19.

    Peñalver A, Pocurull E, Borrull F, Marcé RM (2001) J Chromatogr A 922:377–384

    Article  Google Scholar 

  20. 20.

    Holadová K, Prokupková G, Hajslová J, Poustka J (2007) Anal Chim Acta 582:24–33

    Article  Google Scholar 

  21. 21.

    Serodio P, Nogueira JMF (2004) Anal Chim Acta 517:21–32

    Article  CAS  Google Scholar 

  22. 22.

    Prieto A, Telleira O, Etxebarria N, Fernández LA, Usobiaga A, Zuloaga O (2008) J Chromatogr A 1214:1–10

    Article  CAS  Google Scholar 

  23. 23.

    Gibson R, Wang M-J, Padgett E, Beck AJ (2005) Chemosphere 61:1336–1344

    Article  CAS  Google Scholar 

  24. 24.

    Bonini M, Errani E, Zerbinati G, Ferri E, Girotti S (2008) Michrochem J 90:31–36

    Article  CAS  Google Scholar 

  25. 25.

    Silva MJ, Slakman AR, Reidy JA, Preau JL, Herbert AR, Samandar E, Needham LL, Calafat AM (2004) J Chromatogr B 805:161–167

    Article  CAS  Google Scholar 

  26. 26.

    Li J, Cai Y, Shi Y, Mou S, Jian G (2008) Talanta 74:498–504

    Article  CAS  Google Scholar 

  27. 27.

    Sahitoh T, Matsushima S, Hiraide M (2004) J Chromatogr A 1040:185–191

    Article  Google Scholar 

  28. 28.

    Pérez Feás C, Barciela Alonso MC, Peña Vázquez E, Herbello Hermelo P, Bermejo Barrera P (2008) Talanta 75:1184–1189

    Article  Google Scholar 

  29. 29.

    Hanawa T, Muramatsu E, Asakama K, Tanaka M, Kawano K, Seki T, Juni K, Nakajima S (2000) Int J Pharm 210:109–115

    Article  CAS  Google Scholar 

  30. 30.

    Silva MJ, Malek NA, Hodge CC, Reidy JA, Kato K, Barr DB, Needman LL, Broca JW (2003) J Chromtogr B 789:393–404

    Article  CAS  Google Scholar 

  31. 31.

    Takatori S, Kitagawa Y, Kitagawa M, Nakazawa H, Hori S (2004) J Chromatogr B 804:397–401

    Article  CAS  Google Scholar 

  32. 32.

    David F., Sandra P., Tienpont B., Vanwalleghem, in C.A., Staples (ED.), The Handbook of Environmental Chemistry. Part Q. Phthalate Esters, vol. 3, Springer, Berlin, 2003, p.15

  33. 33.

    Gimeno RA, Marcé RM, Borrull F (2003) Chromatographia 58:37–41

    CAS  Google Scholar 

  34. 34.

    Serodio P, Nogueira JMF (2006) Water Res 40:2572–2582

    Article  CAS  Google Scholar 

  35. 35.

    Polo M, Llompart M, García-Jares C, Cela R (2005) J Chromatogr A 1072:63–72

    Article  CAS  Google Scholar 

  36. 36.

    Kumar R (1999) A mass spectral guide for quick identification of phthalates esters. American Laboratory, Shelton, p 32

    Google Scholar 

  37. 37.

    Psillakis E, Kalogerakis N (2003) J Chromatogr A 999:145–153

    Article  CAS  Google Scholar 

  38. 38.

    Saito Y, Nakao Y, Imaizumi M, Morishima Y, Kiso Y, Jinno K (2002) Anal Bioanal Chem 373:81–86

    Article  CAS  Google Scholar 

  39. 39.

    Hata N, Yuwatini E, Ando K, Yamada M, Kasahara I, Taguchi S (2004) Anal Sci 20:149–152

    Article  CAS  Google Scholar 

  40. 40.

    Jara S, Lysebo C, Greibokk T, Lundanes E (2000) Anal Chim Acta 407:165

    Article  CAS  Google Scholar 

  41. 41.

    López-Jimenez FJ, Rubio S, Pérez-Bendito D (2005) Anal Chim Acta 551:142–149

    Article  Google Scholar 

  42. 42.

    Cela R (ed) (1994) Avances en Quimiometría práctica. Universidad de Santiago de Compostela, Santiago de Compostela, Spain, p 171

    Google Scholar 

  43. 43.

    Loff S, Kabs F, UIT K, Sartoris J, Mandi B, Niessen KH, Waag KL (2000) J Pediatric Surgery 12:1775–1781

    Article  Google Scholar 

  44. 44.

    Loff S, Subotic U, Reinicke F, Wischmann BJ (2004) J Pediatr Gastroenterol Nutr 39:341–345

    Article  CAS  Google Scholar 

  45. 45.

    Subotic U, Animan T, Kiss M, Brade J, Breitkopf K, Loff S (2007) J Pediatr Gastroenterol Nutr 44:71–76

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors wish to thank the Xunta de Galicia (Grupo de Referencia Competitivos 2007 (000047-0)) for financial support. We are also grateful to the Neonatology Service and the Pharmacy Department from Complejo Hospitalario Universitario de Santiago, CHUS, for supplying the parenteral nutrition. Cristina Pérez Feás wishes to thank the Ministerio de Educación y Ciencia for her FPU grant.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Pilar Bermejo-Barrera.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Pérez-Feás, C., Barciela-Alonso, M.C., Sedes-Díaz, A. et al. Phthalates determination in pharmaceutical formulae used in parenteral nutrition by LC-ES-MS: importance in public health. Anal Bioanal Chem 397, 529–535 (2010). https://doi.org/10.1007/s00216-009-3337-0

Download citation

Keywords

  • Phthalates
  • LC-ES-MS
  • Parenteral nutrition