Optimization of the extraction method for the determination of methadone and its metabolite EDDP in urine by gas chromatography

Česká verze

Authors: R. Horáková; J. Valentová; I. Pechová; F. Devínsky
Authors place of work: Univerzita Komenského Bratislava, Farmaceutická fakulta, Katedra chemickej teórie liečiv
Published in the journal: Čes. slov. Farm., 2008; 57, 265-268
Category: Původní práce

Summary

The present study aimed to develop a suitable extraction method for the determination of methadone and it’s metabolite EDDP in human urine by gas chromatography with a nitrogen–phosphorus detector (NPD). The extraction method was optimized in an effort to receive the most satisfactory yield of the mentioned compounds from human urine. The highest yields were obtained by alkaline extraction (~ pH 9) with dietylether. Proadiphene (PA) was used as the internal standard. The most efficient yields were determined as follows: 91 ± 5 % for methadone (MTD) and 86 ± 5 % for its metabolite EDDP. The detection limit (LOD) of MTD was 8 ng/ml, for EDDP 23 ng/ml, and the limit of quantification (LOQ) was 27 ng/ml of MTD and for EDDP 77 ng/ml. The accuracy of this method inter day was found for MTD 1.1–2.32 %, for EDDP 7.3–9.3 % and intra day for MTD it was 9.1–13.7 %, for EDDP 4.7–8.7 %. The suitability of the developed method was checked for routine monitoring of MTD and it’s metabolite EDDP in human urine for 5 different samples taken from methadone maintenance program.

Key words:
methadone (MTD) – 2-ethylidene-3,3-diphenyl-1,5-dimethylpyrrolidine (EDDP) – urine – GC/NPD

Zdroje

1. Pothier, J., Galand, N.: J. Chromatogr. A, 2005; 1080, 186–191.

2. Whelan, G., Lintzeris, N., McDonough, M. et al.: Methadone guidelines prescribers and pharmacists. 1. vydanie. Melbourne: State of Victoria, 2000; 7–15.

3. Kreek, M. J., Ann, N. Y.: Acad. Sci., 2000; 909, 186.

4. Eap, CH. B., Buclin, T., Bacmann, P.: Clin. Pharmacokinet., 2002; 41, 1153–1193.

5. Habrdová, V., Balíková, M.: Chem. Listy, 2002; 96, 1006–1009.

6. Misztal, G.: Acta Pol. Pharm., 1990; 47(5–6), 5–8.

7. Digiusto, E., Seres, V., Bibb, Z. A., Batey, R.: Addict. Behav., 1996; 21, 319–329.

8. Adams, P. S., Haines-Nutt, R. F.: J. Chromatogr., 1985; 329, 438–440.

9. Pierce, T. L., Murray, A. G. W., Hoff, W.: Science, 1992; 30, 443–447.

10. Choo, R. E., Murphy, C. M., Jones, H. E., Huestis, M. A.: J. Chromatogr. B, 2005; 814, 369–373.

11. Quintela, O., López, P., Bermejo, A.M., López-Rivadulla, M.: J. Chromatogr. B, 2006; 834, 188–194.

12. Müller, K.: Pharmazie, 1983; 38, 596–601.

13. Georgakopoulos, C. G., Kiburis, J. C.: Anal. Chem., 1991; 63, 2021–2004.

14. Schmidt, N., Still, R., Brune, K., Geisslinger, G.: Pharm. Research, 1993; 10 (3), 441–444.