Determination of hydralazine in human plasma by high-performance liquid chromatography with electrochemical detection

Hydralazine is used as an antihypertensive vasodilator drug. A specific and sensitive method for extraction and analysis of hydralazine by high-performance liquid chromatography (HPLC) with electrochemical detection was developed. Hydralazine and 4-methylhydralazine (internal standard) in plasma were derivatized at room temperature with salicylaldehyde. The derivatives were extracted in basic medium with a mixture of heptane, methylene chloride and isopentyl alcohol. A very good separation of hydralazine and 4-methylhydralazine from matrix material was achieved on a Supelcosil LC-18-DB (5 microns) reversed-phase column kept at 28 degrees C with a mobile phase of 66% methanol in 0.055 M citric acid/0.02 M dibasic sodium phosphate (pH 2.5). The hydralazine level was measured electrochemically by a screen oxidation mode. This method offers significant advantages in sensitivity, specificity and accuracy. Sample analysis by HPLC required less than 8 min. Application of the method to monitor plasma levels of hydralazine from a patient receiving the drug for the treatment of severe pregnancy-induced hypertension is discussed.