Microsomal stability and metabolite profiling

Lim, H. K., Chan, K. W., Sisenwine, S., and Scatina, J. A. (2001). Simultaneous screen for microsomal stability and metabolite profile by direct injection turbulent-laminar flow LC-LC and automated tandem mass spectrometry. Anal. Chem. 73 2140-2146. 

Lim,H.K. Chan, K.W. Sisenwine, S. Scatina, J.A. Simultaneous Screen for Microsomal Stability and Metabolite Profile by Direct Injection Turbulent-laminar Flow LC-LC and Automated Tandem Mass Spectrometry, Anal. Chem. 73(9), 2140-2146 (2001). 

Gu, M. Lim, H.K. An Intelligent Data Acquisition System for Simultaneous Screening of Microsomal Stability and Metabolite Profiling by Liquid Chromatography/Mass Spectrometry, 7. Mass Spectrom. 36(9), 1053-1061 (2001). 

Gu M, Lim HK. An intelligent data acquisition system for simultaneous screening of microsomal stability and metabolite profiling by liquid chromatography/mass spectrometry. J Mass Spectrom 2001 36 1053-1061. 

Gu and Lim [76] described the use of DDA for microsomal stability studies and metabolite profiling. First, the relevant m/z of an unknown lead compounds is determined. This information is used in SIM experiments for quantitation. Once the peak area of the compoimd tested falls below a certain threshold, e.g., 60% of the initial value, data-dependent product-ion MS-MS analysis is performed for metabolite identification. Some results for adatanserin are shown in Figure 10.11. 

Figure 10.11 Results for adatanserin of (a) a microsomal metabolite stability study, and (b) the metabolite profiling study performed after 10 min incubation. Metabolites Ml and M2 are dihydroxy-analogues, M3, M4, M5, and M9 are hydroxy-analogues, and M6, M7, and M8 still have to be identified. Reprinted from [76] with permission. 2001, John Wiley Sons, Ltd.

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