High-throughput solid-phase extraction for the determination of cimetidine in human plasma

Area of Science:

• Analytical Chemistry
• Pharmacokinetics

Background:

• Manual solid-phase extraction (SPE) methods can be time-consuming for large sample volumes.
• Automated systems are needed to increase throughput in bioanalytical laboratories.

Purpose of the Study:

• To implement and validate a high-throughput automated SPE system for cimetidine analysis in human plasma.
• To compare the performance of the automated method with a previously validated manual method.

Main Methods:

• Adaptation of a manual SPE method for cimetidine using 96-well Microlute extraction plates (50 mg Varian C18 sorbent).
• Automated sample cleanup performed by a pipetting robot.
• Separation by reversed-phase high-performance liquid chromatography (HPLC) with UV detection at 234 nm.

Main Results:

• The automated SPE method demonstrated adequate linearity, specificity, precision, and accuracy within the validated calibration range (0.100–5.00 mg/l).
• Inaccuracy and imprecision were below 20% across all concentration levels.
• Good correlation was observed between the automated and manual methods in cross-check analysis of clinical trial samples.
• Average sample preparation time decreased from approximately 4 minutes to 0.6 minutes per sample.
• Achieved a sample throughput of at least 160 samples per day, limited by HPLC analysis time.

Conclusions:

• The automated high-throughput SPE system is a reliable and efficient method for cimetidine analysis in human plasma.
• The system significantly reduces hands-on time and increases sample throughput compared to manual methods.
• This automation is suitable for bioanalytical applications, particularly in clinical trials.