PMID- 11816004
OWN - NLM
STAT- MEDLINE
DCOM- 20020402
LR  - 20171116
IS  - 0269-3879 (Print)
IS  - 0269-3879 (Linking)
VI  - 16
IP  - 1
DP  - 2002 Feb
TI  - Determination of (3S)-3-hydroxy quinidine for metabolism screening experiments 
      using direct injection capillary electrophoresis and laser-induced fluorescence 
      detection.
PG  - 1-6
AB  - Capillary electrophoresis (CE) has been used with collinear laser-induced 
      fluorescence detection (LIF) to determine the amount of (3S)-3-hydroxy quinidine 
      (3OHQ) formed on direct injection of microsomal incubation mixtures. 3OHQ is the 
      CYP 3A4 metabolite of quinidine sulfate (QS) and is therefore useful for 
      metabolism screening studies. The method was validated analytically and tested 
      for its capability of screening for a weak inhibitor of the CYP 3A4 isozyme. A 
      linear calibration was found to provide the best fit for the standard curve with 
      a correlation of 0.9950 and all concentration residuals less than 15%. The 
      percentage relative standard deviations (RSDs) of two controls, 175 and 2250 
      ng/mL, were 9.29 and 5.68% and the percentage differences from normal (DFN) were 
      6.87 and -4.37%, respectively. The concentration limit of detection (LOD) for 
      3OHQ in the incubation matrix was 52.11ng/mL and the mass LOD was approximately 
      521.1 fg (injection volume 10 nL). The effectiveness of the method to screen for 
      the weak inhibitor erythromycin has been shown by calculating percentage 
      inhibition when incubating with different concentrations of QS. Sensitive 
      detection coupled with the convenience of the direct injection technique makes 
      this an attractive approach for metabolism screening. The small sample size 
      capability of CE will further reduce the quantities of probe drug, microsomes and 
      other reagents required for incubation studies.
CI  - Copyright 2001 John Wiley & Sons, Ltd.
FAU - Bhoopathy, S
AU  - Bhoopathy S
AD  - Department of Pharmaceutics, Medical College of Virginia, Virginia Commonwealth 
      University, Richmond, VA 23298-0533, USA.
FAU - Karnes, H T
AU  - Karnes HT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biomed Chromatogr
JT  - Biomedical chromatography : BMC
JID - 8610241
RN  - 0 (Enzyme Inhibitors)
RN  - 00G939C83O (3-hydroxyquinidine)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - EC 1.- (Mixed Function Oxygenases)
RN  - EC 1.14.14.1 (CYP3A protein, human)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP3A)
RN  - ITX08688JL (Quinidine)
SB  - IM
MH  - Animals
MH  - Cytochrome P-450 CYP3A
MH  - Cytochrome P-450 Enzyme System/metabolism
MH  - Electrophoresis, Capillary/*methods
MH  - Enzyme Inhibitors/analysis
MH  - Lasers
MH  - Microsomes, Liver/enzymology
MH  - Mixed Function Oxygenases/metabolism
MH  - Quinidine/*analogs & derivatives/*metabolism
MH  - Rats
MH  - Reference Standards
MH  - Reproducibility of Results
MH  - Sensitivity and Specificity
MH  - Spectrometry, Fluorescence/*methods
EDAT- 2002/01/30 10:00
MHDA- 2002/04/03 10:01
CRDT- 2002/01/30 10:00
PHST- 2002/01/30 10:00 [pubmed]
PHST- 2002/04/03 10:01 [medline]
PHST- 2002/01/30 10:00 [entrez]
AID - 10.1002/bmc.100 [pii]
AID - 10.1002/bmc.100 [doi]
PST - ppublish
SO  - Biomed Chromatogr. 2002 Feb;16(1):1-6. doi: 10.1002/bmc.100.