[Determination of amlodipine in human plasma by liquid chromatography-tandem mass spectrometry]

To develop a sensitive and specific LC/MS/MS method for determination of amlodipine in human plasma.

Amlodipine and internal standard 4'-hydroxypropafenone were extracted from plasma using liquid-liquid extraction, then separated on a Zorbax C8 column. The mobile phase consisted of acetonitrile-water-formic acid (75:35:1), at a flow-rate of 0.4 mL.min-1. A Finnigan TSQ tandem mass spectrometer equipped with electrospray ionization source was used as detector and was operated in the positive ion mode. Selected reaction monitoring (SRM) using the precursor-->product ion combinations of m/z 409-->238 and m/z 358-->116 was used to quantify amlodipine and internal standard, respectively.

The linear calibration curves were obtained in the concentration range of 0.4-16.0 ng.mL-1. The limit of quantification was 0.4 ng.mL-1. Each plasma sample was chromatographed within 3.7 min. The method was successfully used in several pharmacokinetic studies for amlodipine. More than 1,500 plasma samples were assayed within two weeks.

The method is proved to be suitable for clinical investigation of amlodipine pharmacokinetics, which offers advantages of specificity, speed, and greater sensitivity over the previously reported methods.