Abstract
A rapid LC-MS/MS method with good accuracy and sensitivity was developed and validated for the pharmacokinetics study of metoprolol (MP) in beagle dogs. The plasma samples were simply precipitated by methanol and then analyzed by LC-MS/MS. An Ultimate XB-C18 column (150 × 2.1 mm ID, 5 μm) was used for separation, with methanol-water containing 0.2% formic acid (65:35, v/v) as the mobile phase at a flow rate of 0.2 mL/min. Monitoring ions of MP and internal standard (hydroxypioglitazone) were m/z 268.1/115.6 and m/z 373.1/150.2, respectively. The linear range was 3.03–416.35 ng/mL with an average correlation coefficient of 0.9996, and the limit of quantification was 3.03 ng/mL. The intra- and inter-day precision was less than 15%. At low, middle and high concentrations, the recovery, the matrix effect and the accuracy was in the range of 76.06%–95.25%, 93.67%–104.19% and 95.20%–99.96% respectively. The method was applied for the pharmacokinetics study of MP tartrate tablets (50 mg). The AUC0-t, Tmax and Cmax were respectively 919.88 ± 195.67 μg/L·h, 0.96 ± 0.33 h, 349.12 ± 78.04 ng/mL.
Highlights
Metoprolol (MP) is a kind of selective β1-adrenergic receptor blocker which has been widely used to treat hypertension, angina pectoris, arrhythmia, myocardial infarction and other cardiovascular diseases in the clinic
The selectivity of LC-MS/MS method was investigated by comparing chromatograms of drug-free plasma, drug-free plasma spiked with MP and ion spray voltage (IS), and plasma samples obtained after drug dosing
The results indicated that MP was stable in both untreated and post-preparative beagle dog plasma samples over all steps of the analysis
Summary
Metoprolol (MP) is a kind of selective β1-adrenergic receptor blocker which has been widely used to treat hypertension, angina pectoris, arrhythmia, myocardial infarction and other cardiovascular diseases in the clinic. The pharmacokinetics behaviour of MP in different dosage forms is important for providing reference to its clinical use and pharmaceutical formulation research. The LC-MS/MS [13,14,15,16,17,18,19] method has been applied in some research to measure MP concentration in plasma due to the short analysis period and high selectivity. We treated the plasma samples by a simple protein precipitation method and developed a fast, sensitive and accurate LC-MS/MS method for quantitative analysis of MP in beagle dogs. The method was fully validated and subsequently applied to the pharmacokinetics study of MP tartrate tablets to verify its availability in the non-clinical pharmacokinetics study of MP formulations
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