Determination of metoprolol tartrate and bisoprolol fumarate by capillary electrophoresis coupled with tris(2,2′-bipyridyl)-ruthenium(ii) electrochemiluminescence detection and study on the interaction between the drugs and human serum albumin

Abstract

A new method for separation and determination of metoprolol tartrate (ME) and bisoprolol fumarate (BF) by capillary electrophoresis (CE) coupled with tris(2,2′-bipyridyl)-ruthenium(II) electrochemiluminescence (ECL) detection was developed. The parameters including the pH and concentration of the running buffer, separation voltage and detection potential that affect CE separation and ECL detection were optimized. Under the optimized conditions, ME and BF were well separated and detected within 10 min, the limits of detection (LODs S/N = 3) are 1.9 × 10⁻⁸ mol L⁻¹ for ME and 9.4 × 10⁻⁸ mol L⁻¹ for BF, separately. The RSDs of the peak area of ME and BF (n = 3) are 2.1% and 3.8% within a day (intraday), and 3.1% and 5.5% in 3 consecutive days (interday). The RSDs of the migration time of ME and BF are 4.5 and 6.7% for intraday, and 7.4 and 7.9% for interday. The limits of quantitation (LOQs S/N = 10) in human urine samples are 3.3 × 10⁻⁷ mol L⁻¹ for ME and 1.4 × 10⁻⁶ mol L⁻¹ for BF. The recoveries (n = 3) of ME and BF in human urine are from 89.0 to 126.0% with less than 7.4% in RSD. This method was also successfully applied to the determination of ME and BF in human urine and study on the interaction between ME or BF and human serum albumin (HSA). The number of binding sites of ME and BF with HSA is 1.2 and 1.1, and the binding constants are 2.8 × 10³ and 2.7 × 10³ L mol⁻¹, respectively.