Document Detail


Simultaneous RP-HPLC-DAD quantification of bromocriptine, haloperidol and its diazepane structural analog in rat plasma with droperidol as internal standard for application to drug-interaction pharmacokinetics.
MedLine Citation:
PMID:  19908205     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A simple and rapid RP-HPLC-DAD method was developed and validated for simultaneous determination of the dopamine antagonists haloperidol, its diazepane analog, and the dopamine agonist bromocriptine in rat plasma, to perform pharmacokinetic drug-interaction studies. Samples were prepared for analysis by acetonitrile (22.0 microg/mL) plasma protein precipitation with droperidol as an internal standard, followed by a double-step liquid-liquid extraction with hexane : chloroform (70:30) prior to C-18 separation. Isocratic elution was achieved using a 0.1% (v/v) trifluoroacetic acid in deionized water, methanol and acetonitrile (45/27.5/27.5, v/v/v). Triple-wavelength diode-array detection at the lambda(max) of 245 nm for haloperidol, 254 nm for the diazepane analog and droperidol, and 240 nm for bromocriptine was carried out. The LLOQ of DAL, HAL, and BCT were 45.0, 56.1, and 150 ng/mL, respectively. In rats, the estimated pharmacokinetic parameters (i.e., t(1/2), CL, and V(ss)) of HAL when administered with DAL and BCT were t(1/2) = 16.4 min, V(ss) = 0.541 L/kg for HAL, t(1/2) = 28.0 min, V(ss) = 2.00 L/kg for DAL, and t(1/2) = 24.0 min, V(ss) = 0.106 L/kg for BCT. The PK parameters for HAL differed significantly from those previously reported, which may be an indication of a drug-drug interaction.
Authors:
Johnique Billups; Cynthia Jones; Tanise L Jackson; Seth Y Ablordeppey; Shawn D Spencer
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Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Biomedical chromatography : BMC     Volume:  24     ISSN:  1099-0801     ISO Abbreviation:  Biomed. Chromatogr.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-21     Completed Date:  2010-09-17     Revised Date:  2013-07-22    
Medline Journal Info:
Nlm Unique ID:  8610241     Medline TA:  Biomed Chromatogr     Country:  England    
Other Details:
Languages:  eng     Pagination:  699-705     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2009 John Wiley & Sons, Ltd.
Affiliation:
Biopharmaceutics Laboratory, Division of Basic Sciences, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307 USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bromocriptine / blood*,  chemistry,  pharmacokinetics
Chromatography, High Pressure Liquid / instrumentation,  methods*,  standards
Droperidol / analysis*
Drug Interactions
Drug Stability
Haloperidol / blood*,  chemistry,  pharmacokinetics
Molecular Structure
Rats
Rats, Sprague-Dawley
Reference Standards
Grant Support
ID/Acronym/Agency:
1 C06-RR12512-01/RR/NCRR NIH HHS; G12 RR 03020/RR/NCRR NIH HHS; G12 RR003020/RR/NCRR NIH HHS; G12 RR003020-20/RR/NCRR NIH HHS; G12 RR003020-26/RR/NCRR NIH HHS; GM 08111/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
25614-03-3/Bromocriptine; 52-86-8/Haloperidol; 548-73-2/Droperidol
Comments/Corrections

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