A LC-MS/MS Quantification of Moxonidine in Plasma

Abstract

Introduction: Moxonidine is a new generation centrally acting antihypertensive drug for the treatment of mild to moderate essential hypertension. It may play a role when thiazides, beta-blockers, ACE inhibitors, and calcium channel blockers are inappropriate or fail to control blood pressure. It demonstrates beneficial effects on the parameters of the insulin resistance syndrome, apparently independent of blood pressure reduction. Moxonidine is a selective imidazoline receptor subtype 1 agonist. This receptor subtype is found in both the rostral ventro-lateral pressor region and the ventromedial depressor region of the medulla oblongata. Objectives: quantification of Moxonidine antihypertensive drug in plasma using hyphenated analytical technique LC-MS/MS.

Methods: To determine the plasma concentrations of moxinidine by liquid chromatography in conjunction with a triple quad mass spectrometer (LC-MS/MS) using an internal method. The development of the method was conducted in such a way that sufficient sensitivity was achieved and no short-term and long-term matrix effects affected the performance of the method. Sensitivity was found to be better with positive ionization than with negative ionization.

Results: The sum of multiple daughter ions was used as mass transactions for moxonidine are 242.05/206.1 and 242.05/199.05 where as single mass transaction was used for clonidine are 230.1/213.1. Chromatography was optimized using acetonitrile:buffer (10 mmol ammonium acetate) (75:25) on a Hypurity C8 analytical column, 100 x 4.6 mm. Calibration curve found to be linear over the range 5.004 to 10345.023 pg/ml using 1/x2 as weighting factor.

 Conclusions: The method is successfully applied to the analysis of 360 clinical trial samples collected after administration of 25 mg of moxonidine in a two-phase IEC-approved clinical trial. The resulting sample was reanalyzed and the method found is reproducible.