Cimetidine assay in human plasma by liquid chromatography

Area of Science:

• Pharmacokinetics
• Analytical Chemistry
• Clinical Pharmacology

Background:

• Cimetidine is a widely used medication requiring accurate plasma concentration monitoring.
• Previous methods for cimetidine determination may have limitations in accuracy or sensitivity.
• In vitro sulphoxidation in whole blood necessitates plasma-based assays for reliable results.

Purpose of the Study:

• To develop and validate a sensitive and accurate liquid chromatography assay for determining cimetidine concentrations in human plasma.
• To investigate the pharmacokinetic profile of orally administered cimetidine in human volunteers.
• To establish the correlation between minimum plasma cimetidine levels and the area under the time-concentration curve.

Main Methods:

• Extraction of cimetidine from alkalized human plasma using ethyl acetate.
• Purification through acid wash and re-extraction into ethyl acetate.
• Analysis via liquid chromatography with detection.
• Pharmacokinetic study involving oral administration of cimetidine to human volunteers and serial blood sampling.

Main Results:

• The developed assay demonstrated high accuracy (within 3%) and a low limit of sensitivity (0.1 mg/l) using 750 microliters of plasma.
• In vitro sulphoxidation was observed in whole blood, confirming the suitability of plasma for the assay.
• A significant correlation (r = 0.96) was found between the average minimum plasma cimetidine concentration and the mean area under the time-concentration curve over three dose intervals.

Conclusions:

• The described liquid chromatography assay is accurate and sensitive for quantifying cimetidine in human plasma.
• The assay is suitable for pharmacokinetic studies due to its reliability and ability to detect low concentrations.
• Minimum plasma cimetidine concentrations provide a reliable indicator of overall drug exposure in patients.