Microdialysis combined with liquid chromatography-tandem mass spectrometry for the determination of nimodipine in the guinea pig hippocampus

• The pharmacokinetic behavior of nimodipine in guinea pig hippocampus was determined.
• Microdialysis technique was used for sample collection.
• A rapid and sensitive LC–MS/MS method was developed and validated.
• The method was sensitive with a LLOQ of 0.2 ng/ml for nimodipine.

Nimodipine is a dihydropyridine calcium-channel blocker that has been recently shown to be effective on the function of central nervous system. It has been reported that treatment against deficits of learning and memory in animals and human by maintain the calcium homeostasis in hippocampus with nimodipine may be promising therapeutic strategies. A rapid and sensitive liquid chromatography-tandem mass spectrometric method was developed to determination the nimodipine in hippocampus using microdialysis technique. The separation was accomplished on an Agilent Zorbax SB-C18 column (100 mm × 2.1 mm ID, 3.5 μm) with the mobile phase composed of methanol-water (80:20, v/v) containing 0.2% formic acid at a flow rate of 0.2 ml/min. Multiple reaction monitoring of the precursor-product ion transitions 419 → 343 for nimodipine and 361 → 315 nitrendipine (IS) was used for quantitation. The method was sensitive with a lower limit of quantitation (LLOQ) of 0.2 ng/ml for nimodipine, with good linearity in the range of 0.2–20 ng/ml. All the validation data, such as accuracy, precision, intra- and inter-day repeatability and stability were within the required limits. The method was successfully applied to p harmacokinetic study of the nimodipine in the guinea pig hippocampus.