*3.6. Data Analysis*

Peaks were extracted using the automatic integration software MasterHands (Keio University, Tsuruoka, Japan) in order to obtain peak information, including *<sup>m</sup>*/*<sup>z</sup>*, migration time for CE-TOFMS measurement (MT), and peak area [31]. Signal peaks corresponding to isotopomers, adduct ions, and other product ions of known metabolites were excluded, and the remaining peaks were annotated

with putative metabolites from the HMT metabolite database based on their MTs and *m*/*z* values determined by TOFMS. The tolerance range for the peak annotation was configured at ±0.5 min for MT and ±10 ppm for *<sup>m</sup>*/*<sup>z</sup>*. In addition, peak areas were normalized against those of the internal standards and then the resultant relative area values were further normalized by the sample amount. HCA and PCA were performed using HMT's proprietary software, PeakStat and SampleStat, respectively. The detected metabolites were plotted on metabolic pathway maps by using the VANTED (Visualization and Analysis of Networks containing Experimental Data) software [32].
