Identification of oxidative degradates of the thrombin inhibitor, 3-(2-phenethylamino)-6-methyl-1-(2-amino-6-methyl-5-methylenecarboxamidomethylpyridinyl)pyrazinone, using liquid chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry

Journal of Pharmaceutical and Biomedical Analysis

Volumn 20, Issue 3, 1999, Pages 471-485

  Wu, Yunhui ^a   Chen, Xin ^a   Gier, Lynn ^a   Almarsson, Örn ^a   Ostovic, Drazen ^a   Loper, Alice E ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Degradates; Isomers; L 375,378; Liquid chromatography mass spectrometry; Oxidation; Tandem mass spectrometry

Indexed keywords

1 (2 AMINO 6 METHYL 5 METHYLENECARBOXAMIDOMETHYLPYRIDINYL) 6 METHYL 3 (2 PHENETHYLAMINO)PYRAZINONE; 1 (6 AMINO 2 METHYL 3 PYRIDINYLMETHYLAMINOCARBONYLMETHYL) 3 PHENETHYLAMINO 6 METHYL 2 PYRAZINONE; HYDROGEN PEROXIDE; THROMBIN INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; DRUG DEGRADATION; DRUG IDENTIFICATION; IN VITRO STUDY; INJECTION; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; OXIDATION; PRIORITY JOURNAL; REACTION ANALYSIS; TABLET;

AMIDES; AMINOPYRIDINES; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; DIAMIDE; DRUG CONTAMINATION; DRUG STABILITY; HYDROGEN PEROXIDE; HYDROXYLATION; MASS SPECTROMETRY; MOLECULAR WEIGHT; OXIDATION-REDUCTION; PYRAZINES; REPRODUCIBILITY OF RESULTS; SOLUTIONS; SPECTROPHOTOMETRY, ULTRAVIOLET; TABLETS; THROMBIN;

EID: 0033013546     PISSN: 07317085     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0731-7085(99)00035-7     Document Type: Article

References (24)

1. P.E.J. Sanderson, The design of orally active pyridinone and pyrazinone acetamide thrombin inhibitors, Presented at the 215th ACS National Meeting, Dallas, TX, March 1998.
2. L. Gier, Ö. Almarsson, D. Ostovic, The stressed formulation samples and the reaction mixture of L-375,378 with hydrogen peroxide were analyzed by HPLC with a diode array detector using various elution conditions. The retention time and UV spectra of the degradates observed in the stressed formulations were matched with those for the reaction products, unpublished results.
3. Rourick R.A., Volk K.J., Klohr S.E., Spears T., Kerns E.H., Lee M.S. J. Pharm. Biomed. Anal. 14:1996;1743-1752.
4. Qin X.-Z., Ip D.P., Chang K.H.-C., Dradransky P.M., Brooks M.A., Sakuma T. J. Pharm. Biomed. Anal. 12:1994;221-233.
5. Qin X.-Z., Tsai E.W., Sakuma T., Ip D.P. J. Chromatogr. A. 686:1994;205-212.
6. Andre M., Domanig R., Riemer E., Moser H., Groeppelin A. J. Chromatogr. A. 741:1996;146.
7. Volk K.J., Klohr S.E., Rourick R.A., Kerns E.H., Lee M.S. J. Pharm. Biomed. Anal. 14:1996;1663-1674.
8. Ramsey E.D., Lawrence S.D., Games D.E., Hewlins M.J.E., McDowall M.A. Anal. Commun. 33:1996;79-83.
9. Goosen E.C., Stegman K.H., de Jong D., de Jong G.J., Brinkman U.A.T. Analyst. 121:1996;61-66.
10. Silvestro L., Savu S.R. Rapid Commun. Mass Spectrom. 10:1996;151-156.
11. Almudaris A., Ashton D.S., Ray A., Valko K. J. Chromatogr. A. 689:1995;31-38.
12. Malkki-Laine L., Bruins A.P. J. Pharm. Biomed. Anal. 12:1994;543-550.
13. Ogorka J., Schwinger G., Bruat G., Seidel V. J. Chromatogr. 626:1992;87-96.
14. Lee M.S., Kerns E.H., Hail M.E., Liu J., Volk K.J. Liq. Chromatogr. Gas Chromatogr. 15:1997;542-558.
15. Wilson S.R., Wu Y. Org. Mass Spectrom. 29:1994;186-191.
16. Wilson S.R., Wu Y. J. Am. Soc. Mass Spectrom. 4:1993;596-603.
17. Wilson S.R., Wu Y. Organometallics. 12:1993;1478-1480.
18. Wilson S.R., Wu Y. J. Am. Chem. Soc. 115:1993;10334-10337.
19. Wilson S.R., Kaprinidis N., Wu Y., Schuster D.J. J. Am. Chem. Soc. 115:1993;8495-8496.
20. Bateman K.P., Locke S.J., Volmer D.A. J. Mass Spectrom. 32:1997;297-304.
21. Feistner G.J. J. Mass Spectrom. 30:1995;1546-1552.
22. Josephs J.L. Rapid Commun. Mass Spectrom. 10:1996;1333-1344.
23. Gillespie T.A., Lindsay T.J., Cornpropst J.D., Bonate P.L., Skaggs T.G., DeLong A.F., Shipley L.A. ACS Symp. Ser. 619:1996;315-329.
24. Porter Q.N. Mass Spectrometry of Heterocyclic Compounds. 2nd ed:1985;Wiley, New York.