( e specific structural assignment ...)In-Vitro Metabolism Studies Using Data-Dependent LC/MSn

e specific structural assignment, a further LC/MSⁿ experiment was performed using negative ion mode. These data are summarized in Scheme 3. The ions observed at m/z 323, 198 and 134 indicate that structure C in Figure 6 was incorrect. Thus only two LC/MSⁿ experiments enabled the novel metabolite at 23.87 min to be identified as hydroxylation of the ethyl chain at either the benzylic position, or alpha to the amide nitrogen (structures A and B in Figure 6).


Figure 6. Possible structures of metabolite at 23.87 min.



Scheme 3.

Conclusions

With the use of Data-Dependent MS¹/MS²/MS³ analyses seven metabolites of glyburide were structurally characterized within two LC/MS analyses. This approach not only afforded molecular weight, retention time, and structural information with greater specificity than LC/MS and LC/MS/MS using a triple quadrupole, but reduced the analysis time.

REFERENCES

1. Glibenclamide, Therapeutic Drugs, Ed. Collin Dollery, Churchill Livingstone, New York, NY (1991) G21-G26.

2. D.G. Kaiser and A.A. Forist, A review of Glyburide metabolism in man and laboratory animals, Micronase: Pharmacological and Clinical Evaluation, Ed. H. Rifkin et. al., Excerpta Medica Foundation International Congress Series No. 382, Princeton, NJ. (1975) 31-41W.

3. Clarke, SE, Ayrton, AD and Chenery, RJ., Xenobiotica, 24 (1994) 517-526.




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