Abstract
A sensitive and reproducible liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of amlodipine in human plasma, with gliclazide as an internal standard (IS). The analyte was extracted with ethyl acetate and analyzed on a Diamond C18 (150 mm× 4.6 mm, 5 μm) column. The mobile phase was composed of methanol ?10 mM ammonium acetate with gradient flow rates and gradient conditions. Amlodipine and IS were ionized by positive ion pneumatically assisted electrospray and detected in the multi-reaction monitoring (MRM) mode using precursor→productions of m/z 409.2→238.1, 294.1 and m/z 324.2→127.3, respectively. The specificity, matrix effect, recovery, sensitivity, linearity, accuracy, precision, and stabilities were all validated over the concentration range of 0.05 - 12 ng/mL. The 90% confidence interval (CI) for AUC0-t, AUC0-∞ and Cmax ratios (test: reference) were all within 80% - 125% interval proposed by FDA. It is concluded that the validated method can successfully fulfill the requirement of clinical bioequivalence study of amlodipine in healthy Chinese subjects after administration of amlodipine/losartan combination tablets and amlodipine tablets, and the test and reference tablets were bioequivalent.
Highlights
IntroductionCalcium channel blockers have been widely used in the treatment of hypertension and angina pectoris, and combination therapy with an angiotensin II receptor blocker would enhance antihypertensive activity with greater efficacy and better tolerability, which maximize the blood pressure-lowering effects and minimize the severity of their side effects of each component [1,2,3]
Calcium channel blockers have been widely used in the treatment of hypertension and angina pectoris, and combination therapy with an angiotensin II receptor blocker would enhance antihypertensive activity with greater efficacy and better tolerability, which maximize the blood pressure-lowering effects and minimize the severity of their side effects of each component [1,2,3].Losartan is an active and highly specific non-peptide angiotensin II receptor blocker for the treatment of hypertension and heart failure
The assays of amlodipine in human plasma were validated for assay specificity, matrix effect, recovery, sensitivity, linearity, precision, accuracy, and stability according to the US Food and Drug Administration (FDA) [26] and Chinese State Food and Drug Administration (SFDA) guidelines for the validation of bioanalytical methods
Summary
Calcium channel blockers have been widely used in the treatment of hypertension and angina pectoris, and combination therapy with an angiotensin II receptor blocker would enhance antihypertensive activity with greater efficacy and better tolerability, which maximize the blood pressure-lowering effects and minimize the severity of their side effects of each component [1,2,3]. Losartan is an active and highly specific non-peptide angiotensin II receptor blocker for the treatment of hypertension and heart failure. Chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6methyl-1,4-dihydropyridine (Figure 1(a)), is a potent calcium channel blocker used for the treatment of hypertension and angina pectoris. It has high bioavailability, large volume of distribution and long elimination halflife (t1/2) ranging from 35 to 45 h [6,7]. It has been reported that low plasma amlodipine concentrations are achieved after oral administration [8], a sensitive and specific analytical method is essential for determination of amlodipine in human plasma
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