TABLE 1

Structures of the cytochrome P450 3A4 substrates and metabolites used for the study and the standard curve slope ratio of metabolite to substrate

Embedded Image

R1Substrate R2SubstrateMetabolite R2MetaboliteSlope Ratio
ESIaCSIb
Embedded ImageOCH31OH1M0.71.3
N(CH3)22NH(CH3)2M0.90.4
H3OH3M1.50.9
CH34CH2OH4M2.60.5
Embedded ImageOCH35OH5M1.73.6
N(CH3)26NH(CH3)6M2.50.7
H7OH7M4.01.2
CH38CH2OH8M2.50.5
Embedded ImageOCH39OH9M2.41.9
N(CH3)210NH(CH3)10M1.30.5
H11OH11M2.10.9
CH312CH2OH12M2.20.7
Embedded ImageOCH313OH13M2.31.6
N(CH3)214NH(CH3)14M2.73.0
H15OH15M3.10.8
CH316CH2OH16M2.41.2
Embedded ImageOCH317OH17M3.01.2
N(CH3)218NH(CH3)18M0.6N.D.
H19OH19M2.70.7
CH320CH2OH20M0.92.8
  • N.D., not determined.

  • a Slope (average) of the standard curve for metabolite versus internal standard divided by slope (average) of the standard curve for substrate versus internal standard using ESI.

  • b Slope (average) of the standard curve for metabolite versus internal standard divided by slope (average) of the standard curve for substrate versus internal standard using nanospray ionization. Slopes are presented in the supplemental data.