Journal of Zhejiang University SCIENCE B
ISSN 1673-1581(Print), 1862-1783(Online), Monthly

2008   Vol. 9   No. 5   p. 385~390

Characterization of impurities in the bulk drug lisinopril by liquid chromatography/ion trap spectrometry

Pei-xi ZHU¹, Dan-hua WANG¹, Cui-rong SUN^†‡1, Zhi-quan SHEN^†‡2

(¹Department of Chemistry, Zhejiang University, Hangzhou 310027, China)
(²Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China)
^‡ Corresponding Author
^†E-mail: suncuirong@zju.edu.cn; zhiquan_shen@163.com
Received Jan. 24, 2008; revision accepted Apr. 6, 2008

Abstract: Two trace impurities in the bulk drug lisinopril were detected by means of high-performance liquid chromatography coupled with mass spectrometry (HPLC/MS) with a simple and sensitive method suitable for HPLC/MSⁿ analysis. The fragmentation behavior of lisinopril and the impurities was investigated, and two unknown impurities were elucidated as 2-(6-amino-1-(1-carboxyethylamino)-1-oxohexan-2-ylamino)-4-phenylbutanoic acid and 6-amino-2-(1-carboxy-3-phenylpro-pylamino)-hexanoic acid on the basis of the multi-stage mass spectrometry and exact mass evidence. The proposed structures of the two unknown impurities were further confirmed by nuclear magnetic resonance (NMR) experiments after preparative isolation.

Key words: Lisinopril, Impurities, High-performance liquid chromatography (HPLC), Multi-stage mass spectrometry (MSⁿ)
doi:10.1631/jzus.B0820031             CLC number: R91

References:

[1] Beasley, C.A., Shaw, J., Zhao, Z., Reed, R.A., 2005. Development and validation of a stability indicating HPLC method for determination of lisinopril, lisinopril degradation product and parabens in the lisinopril extemporaneous formulation. J. Pharm. Biomed. Anal., 37(3): 559-567.

[2] Burinsky, D.J., Sides, S.L., 2004. Mass spectral fragmentation reactions of angiotensin-converting enzyme (ACE) inhibitors. J. Am. Soc. Mass Spectrom., 15(9):1300-1314.

[3] Eveson, D.J., Robinson, T.G., Potter, J.F., 2007. Lisinopril for the treatment of hypertension within the first 24 hours of acute ischemic stroke and follow-up. Am. J. Hypertens., 20(3):270-277.

[4] Florêncio, M.H., Fernandez, M.T., Mira, M.L., Millar, A., Jennings, K.R., 1998. Electrospray mass spectrometry of angiotensin-converting enzyme inhibitors. Rapid Commun. Mass Spectrom., 12(23):1928-1932.

[5] Hiserodt, R.D., Brown, S.M., Swijter, D.F.H., Hawkins, N., Mussinan, C.J., 2007. A study of b₁+H₂O and b₁-ions in the product ion spectra of dipeptides containing N-terminal basic amino acid residues. J. Am. Soc. Mass Spectrom., 18(8):1414-1422.

[6] International Conference on Harmonization, 2003. ICH Harmonized Tripartite Guideline Topic Q3A(R): Impurities in New Drug Substances. Federal Register, US Department of Health and Human Services Food and Drug Administration, Vol. 68, p.6924-6925.

[7] Lee, M.S., Kerns, E.H., 1999. LC/MS applications in drug development. Mass Spectrom. Rev., 18(3/4):187-279.

[8] Leis, H.J., Fauler, G., Raspotnig, G., Windischhofer, W., 1998. Quantitative determination of the angiotensin-converting enzyme inhibitor lisinopril in human plasma by stable isotope dilution gas chromatography/negative ion chemical ionization mass spectrometry. Rapid Commun. Mass Spectrom., 12(21):1591-1594.

[9] Leis, H.J., Fauler, G., Raspotnig, G., Windischhofer, W., 1999. An improved method for the measurement of the angiotensin-converting enzyme inhibitor lisinopril in human plasma by stable isotope dilution gas chromatography/negative ion chemical ionization mass spectrometry. Rapid Commun. Mass Spectrom., 13(8):650-653.

[10] Pei, S., Wang, D., Sun, C., Pan, Y., 2006. Characterization of a novel trace-level impurity in lisinopril using multi-stage mass spectrometry. Eur. J. Mass Spectrom., 12(2): 121-127.

[11] Roepstorff, P., Fohlman, J., 1984. Letter to the editors. J. Biomed. Mass Sprctrom., 11(11):601.

[12] Shinde, V., Trivedi, A., Upadhayay, P.R., Gupta, N.L., Kanase, D.G., Chikate, R., 2007. Identification of a new impurity in lisinopril. J. Pharm. Biomed. Anal., 43(1):381-386.

[13] Wang, D.H., Pei, S.F., Zhou, M.H., Sun, C.R., Pan, Y.J., 2006. Characterization of a novel impurity in bulk drug of lisinopril by multidimensional NMR technique. J. Zhejiang Univ. Sci. B, 7(4):310-313.

[14] Wong, Y.C., Charles, B.G., 1995. Determination of the angiotensin-converting enzyme inhibitor lisinopril in urine using solid-phase extraction and reversed phase high-performance liquid chromatography. J. Chromatogr. B., 673(2):306-310.