Determination of trace level genotoxic impurities in small molecule drug substances using conventional headspace gas chromatography with contemporary ionic liquid diluents and electron capture detection

Journal of Chromatography A

Volumn 1361, Issue , 2014, Pages 217-228

  Ho, Tien D ^a   Yehl, Peter M ^a   Chetwyn, Nik P ^a   Wang, Jin ^a   Anderson, Jared L ^b   Zhong, Qiqing ^a  

^a GENENTECH INC   (United States)

^b UNIVERSITY OF TOLEDO   (United States)

Author keywords

Alkyl aryl halide; Electron capture detector; Genotoxic impurity; Headspace gas chromatography; Ionic liquid; Nitro aromatic compound

Indexed keywords

AROMATIC COMPOUNDS; COST EFFECTIVENESS; DIMETHYL SULFOXIDE; IONIC LIQUIDS; LIQUID CHROMATOGRAPHY; MOLECULES; ORGANIC SOLVENTS; QUALITY CONTROL;

ALKYL/ARYL HALIDE; ELECTRON CAPTURE DETECTORS; GENOTOXIC IMPURITIES; HEADSPACE GAS CHROMATOGRAPHY; NITRO AROMATIC COMPOUNDS;

GAS CHROMATOGRAPHY;

1 (2 CHLORO 5 NITROPHENYL)ETHANONE; 1 BROMO 3 CHLOROPROPANE; 1 BUTYL 1 METHYLPYRROLIDINIUM TETRACYANOBORATE; 1 BUTYL 2,3 DIMETHYLIMIDAZOLIUM BIS[(TRIFLUOROMETHYL)SULFONYL]IMIDE; 1 BUTYL 2,3 DIMETHYLIMIDAZOLIUM TETRAFLUOROBORATE; 1 BUTYL 3 METHYLIMIDAZOLIUM BIS[(TRIFLUOROMETHYL)SULFONYL]IMIDE; 1 BUTYL 3 METHYLIMIDAZOLIUM TETRAFLUOROBORATE; 1 CHLORO 2 NITROBENZENE; 1 NITRONAPHTHALENE; 1,6 DIBROMOHEXANE; 2 CHLORO 5 NITROANILINE; 2 NITROBENZALDEHYDE; 2 NITROFLUORENE; 2,4 DIMETHYLNITROBENZENE; 4 NITROBENZALDEHYDE; AROMATIC NITRO COMPOUND; BENZOTRICHLORIDE; BENZYL BROMIDE; BENZYL CHLORIDE; DIMETHYL SULFOXIDE; HALIDE; IODOBUTANE; IONIC LIQUID; N PROPYL BROMOACETATE; N,N DIMETHYLACETAMIDE; TRIHEXYLTETRADECYLPHOSPHONIUM BIS[(TRIFLUOROMETHYL)SULFONYL]IMIDE; UNCLASSIFIED DRUG; MOLECULAR LIBRARY; MUTAGENIC AGENT;

ARTICLE; CHEMICAL ANALYSIS; CONTROLLED STUDY; DRUG IMPURITY; ELECTRON CAPTURE DETECTION; GAS CHROMATOGRAPHY; GENOTOXICITY; HEADSPACE GAS CHROMATOGRAPHY; HIGH TEMPERATURE; INCUBATION TEMPERATURE; LIMIT OF DETECTION; VALIDATION STUDY; CHEMISTRY; DEVICES; ELECTRON; MOLECULAR LIBRARY; PROCEDURES; TEMPERATURE;

CHROMATOGRAPHY, GAS; ELECTRONS; IONIC LIQUIDS; LIMIT OF DETECTION; MUTAGENS; SMALL MOLECULE LIBRARIES; TEMPERATURE;

EID: 84919679558     PISSN: 00219673     EISSN: 18733778     Source Type: Journal    
DOI: 10.1016/j.chroma.2014.07.099     Document Type: Article

References (45)

1. McGovern T., Jacobson-Kram D. Regulation of genotoxic and carcinogenic impurities in drug substances and products. TrAC: Trends Anal. Chem. 2006, 25:790-795.
2. Müller L., Mauthe R.J., Riley C.M., Andino M.M., Antonis D.D., Beels C., DeGeorge J., De Knaep A.G., Ellison D., Fagerland J.A. A rationale for determining, testing, and controlling specific impurities in pharmaceuticals that possess potential for genotoxicity. Regul. Toxicol. Pharmacol. 2006, 44:198-211.
3. US Food and Drug Administration, Department of Health and Human Services, Center for Drug Evaluation and Research (CDER) Guidance for Industry. Genotoxic and Carcinogenic Impurities in Drug Substances and Products: Recommended Approaches December 2008.
4. European Medicines Evaluation Agency, Committee for Medicinal Products for Human Use, Guideline on the Limits of Genotoxic Impurities, CPMP/SWP/5199/02, London, 28 June 2006.
5. Raman N., Prasad A., Ratnakar Reddy K. Strategies for the identification, control and determination of genotoxic impurities in drug substances: a pharmaceutical industry perspective. J. Pharmaceut. Biomed. 2011, 55:662-667.
6. Sun M., Liu D.Q., Kord A.S. A systematic method development strategy for determination of pharmaceutical genotoxic impurities. Org. Process Res. Dev. 2010, 14:977-985.
7. Robinson D.I. Control of genotoxic impurities in active pharmaceutical ingredients: a review and perspective. Org. Process Res. Dev. 2010, 14:946-959.
8. Thayer A.M. Chemical & Engineering News 2010, 27.
9. Teasdale A., Elder D., Fenner S. Genotoxic Impurities: Strategies for Identification and Control 2010, 221-247. John Wiley & Sons, Inc., Hoboken, New Jersey. A. Teasdale (Ed.).
10. Snodin D.J. Genotoxic impurities: a regulatory toxicology commentary on recent articles in organic process research & development. Org. Process Res. Dev. 2011, 15:1243-1246.
11. Teasdale A., Elder D., Chang S.-J., Wang S., Thompson R., Benz N., Sanchez Flores I.H. Risk assessment of genotoxic impurities in new chemical entities: strategies to demonstrate control. Org. Process Res. Dev. 2013, 17:221-230.
12. Liu D.Q., Sun M., Kord A.S. Recent advances in trace analysis of pharmaceutical genotoxic impurities. J. Pharm. Biomed. 2010, 51:999-1014.
13. Elder D., Teasdale A., Lipczynski A. Control and analysis of alkyl esters of alkyl and aryl sulfonic acids in novel active pharmaceutical ingredients (APIs). J. Pharm. Biomed. 2008, 46:1-8.
14. Singh S., Handa T., Narayanam M., Sahu A., Junwal M., Shah R.P. A critical review on the use of modern sophisticated hyphenated tools in the characterization of impurities and degradation products. J. Pharm. Biomed. 2012, 69:148-173.
15. van Wijk A.M., Niederländer H.A.G., Siebum A.H.G., Vervaart M.A.T., de Jong G.J. A new derivatization reagent for LC-MS/MS screening of potential genotoxic alkylation compounds. J. Pharm. Biomed. 2013, 74:133-140.
16. Wu L., Liu D.Q., Vogt F.G., Kord A.S. Gas-phase derivatization via the Meerwein reaction for selective and sensitive LC-MS analysis of epoxides in active pharmaceutical ingredients. J. Pharm. Biomed. 2011, 56:1106-1111.
17. Elder D.P., Snodin D., Teasdale A. Control and analysis of hydrazine, hydrazides and hydrazones-genotoxic impurities in active pharmaceutical ingredients (APIs) and drug products. J. Pharm. Biomed. 2011, 54:900-910.
18. Vanhoenacker G., Dumont E., David F., Baker A., Sandra P. Determination of arylamines and aminopyridines in pharmaceutical products using in-situ derivatization and liquid chromatography-mass spectrometry. J. Chromatogr. A 2009, 1216:3563-3570.
19. An J., Sun M., Bai L., Chen T., Liu D.Q., Kord A. A practical derivatization LC/MS approach for determination of trace level alkyl sulfonates and dialkyl sulfates genotoxic impurities in drug substances. J. Pharm. Biomed. 2008, 48:1006-1010.
20. Nageswari A., Krishna R.K.V.S.R., Mukkanti K. Low-level quantitation of formaldehyde in drug substance by HPLC-UV. Chromatographia 2012, 75:275-280.
21. Sun M., Bai L., Terfloth G.J., Liu D.Q., Kord A.S. Matrix deactivation: a general approach to improve stability of unstable and reactive pharmaceutical genotoxic impurities for trace analysis. J. Pharm. Biomed. 2010, 52:30-36.
22. Bai L., Sun M., An J., Liu D.Q., Chen T.K., Kord A.S. Enhancing the detection sensitivity of trace analysis of pharmaceutical genotoxic impurities by chemical derivatization and coordination ion spray-mass spectrometry. J. Chromatogr. A 2010, 1217:302-306.
23. Ho T.D., Joshi M.D., Silver M.A., Anderson J.L. Selective extraction of genotoxic impurities and structurally alerting compounds using polymeric ionic liquid sorbent coatings in solid-phase microextraction: alkyl halides and aromatics. J. Chromatogr. A 2012, 1240:29-44.
24. Hinshaw J.V. Headspace sampling. LC GC N. Am. 2011, 29:538-546.
25. Lee C.R., Guivarch F., Van Dau C.N., Tessier D., Krstulovic A.M. Determination of polar alkylating agents as thiocyanate/isothiocyanate derivatives by reaction headspace gas chromatography. Analyst 2003, 128:857-863.
26. Elder D., Lipczynski A., Teasdale A. Control and analysis of alkyl and benzyl halides and other related reactive organohalides as potential genotoxic impurities in active pharmaceutical ingredients (APIs). J. Pharm. Biomed. 2008, 48:497-507.
27. David F., Vanhoenacker G., Sandra P., Jacq K., Baker A. Method selection for trace analysis of genotoxic impurities in pharmaceuticals. LC GC Eur. 2009, 22:552.
28. Sun M., Bai L., Liu D.Q. A generic approach for the determination of trace hydrazine in drug substances using in situ derivatization-headspace GC-MS. J. Pharm. Biomed. 2009, 49:529-533.
29. Strohmeyer H.E., Sluggett G.W. Determination and control of TEMPO, a potentially genotoxic free radical reagent used in the synthesis of filibuvir. J. Pharm. Biomed. 2012, 62:216-219.
30. Hinshaw J.V. Headspace sampling: instrumentation. LC GC N. Am. 2012, 30:42-50.
31. Tan Z.-Q., Liu J.-F., Pang L. Advances in analytical chemistry using the unique properties of ionic liquids. TrAC: Trends Anal. Chem. 2012, 39:218-227.
32. Ho T.D., Yu H., Cole W.T.S., Anderson J.L., Majors R.E. Ionic liquids and their applications in sample preparation. LC GC N. Am. 2013, 31:92. 94, 96, 98, 100, 102, 104-107.
33. Andre M., Loidl J., Laus G., Schottenberger H., Bentivoglio G., Wurst K., Ongania K.-H. Ionic liquids as advantageous solvents for headspace gas chromatography of compounds with low vapor pressure. Anal. Chem. 2005, 77:702-705.
34. Liu F.-H., Jiang Y. Room temperature ionic liquid as matrix medium for the determination of residual solvents in pharmaceuticals by static headspace gas chromatography. J. Chromatogr. A 2007, 1167:116-119.
35. Laus G., Andre M., Bentivoglio G., Schottenberger H. Ionic liquids as superior solvents for headspace gas chromatography of residual solvents with very low vapor pressure, relevant for pharmaceutical final dosage forms. J. Chromatogr. A 2009, 1216:6020-6023.
36. Fredlake C.P., Crosthwaite J.M., Hert D.G., Aki S.N., Brennecke J.F. Thermophysical properties of imidazolium-based ionic liquids. J. Chem. Eng. Data 2004, 49:954-964.
37. Sowmiah S., Srinivasadesikan V., Tseng M.-C., Chu Y.-H. On the chemical stabilities of ionic liquids. Molecules 2009, 14:3780-3813.
38. Green M.D., Schreiner C., Long T.E. Thermal, rheological, and ion-transport properties of phosphonium-based ionic liquids. J. Phys. Chem. A 2011, 115:13829-13835.
39. Awad W.H., Gilman J.W., Nyden M., Harris R.H., Sutto T.E., Callahan J., Trulove P.C., DeLong H.C., Fox D.M. Thermal degradation studies of alkyl-imidazolium salts and their application in nanocomposites. Thermochim. Acta 2004, 409:3-11.
40. Drabløs F., Feyzi E., Aas P.A., Vaagbø C.B., Kavli B., Bratlie M.S., Peña-Diaz J., Otterlei M., Slupphaug G., Krokan H.E. Alkylation damage in DNA and RNA-repair mechanisms and medical significance. DNA Repair 2004, 3:1389-1407.
41. Jenkins G., Doak S., Johnson G., Quick E., Waters E., Parry J. Do dose response thresholds exist for genotoxic alkylating agents?. Mutagenesis 2005, 20:389-398.
42. Kojima T., Tanaka Y., Satouchi M. Correlation between electron capture response and chemical structure for alkyl halides. Anal. Chem. 1976, 48:1760-1762.
43. Poole C.F. Derivatization reactions for use with the electron-capture detector. J. Chromatogr. A 2013, 1296:15-24.
44. Eichenbaum G., Johnson M., Kirkland D., O'Neill P., Stellar S., Bielawne J., DeWire R., Areia D., Bryant S., Weiner S. Assessment of the genotoxic and carcinogenic risks of p-nitrophenol when it is present as an impurity in a drug product. Regul. Toxicol. Pharmacol. 2009, 55:33-42.
45. Rosenkranz H.S., Mermelstein R. Mutagenicity and genotoxicity of nitroarenes: all nitro-containing chemicals were not created equal. Mutat. Res. 1983, 114:217-267.