High-performance liquid chromatography assay using ultraviolet detection for urinary quantification of milrinone concentrations in cardiac surgery patients undergoing cardiopulmonary bypass.

An analytical assay using liquid-liquid extraction and high-performance liquid chromatography with ultraviolet detection was developed for the quantification of total (conjugated and unconjugated) urinary concentrations of milrinone after the inhalation of a 5 mg dose in 15 cardiac patients undergoing cardiopulmonary bypass. Urine samples (700 µL) were extracted with ethyl-acetate and subsequently underwent acid back-extraction before and after deconjugation by mild acid hydrolysis. Milrinone was separated on a strong cation exchange analytical column. The mobile phase consisted of a constant mixture of acetonitrile:tetrahydrofurane-NaH2 PO4 buffer (40:60 v/v, pH 3.0). Thirteen calibration curves were linear in the concentration range of 31.25-4000 ng/mL, using olprinone as the internal standard (r(2) range 0.9911-0.9999, n = 13). Mean milrinone recovery and accuracy were respectively 85.2 ± 3.1% and ≥93%. Intra- and inter-day precisions (coefficients of variation) were ≤5% and ≤8%, respectively. Over a 24 h collection period, the cumulative urinary milrinone recovered from 15 patients was 26.1 ± 7.7% of the nominal 5 mg dose administered. The relative amount of milrinone glucuronic acid conjugate was negligible in the urine of patients undergoing cardiopulmonary bypass This method proved to be reliable, specific and accurate to determine the cumulative amount of total milrinone recovered in urine after inhalation.

Correlation between plasma milrinone concentration and renal function in patients with cardiac disease.

BACKGROUND: The dose of milrinone should be reduced in patients with renal failure. However, there is little data examining the relationship between plasma concentration of milrinone (pCmil) and renal function in intravenous infusion. METHODS: We evaluated the pCmil relative to renal function during intravenous infusion. We enrolled 10 heart failure patients. Milrinone was continuously infused at a rate of 0.2 microg/kg/min. Blood samples were collected at 6, 12, 24, and 48 h after the beginning of infusion. Urine was sampled during the first 24 h to calculate creatinine clearance (CLcr) and renal clearance of milrinone (rCLmil). RESULTS: The pCmil exhibited stability over 6 h after the beginning of infusion. During the first 24 h, CLcr and rCLmil were 62.2+/-30.6 ml/min and 1.67+/-0.77 ml/kg/min (106.2+/-60.3 ml/min), respectively. The rCLmil was highly correlated with CLcr. Y=1.77X-3.89 (X, CLcr; Y, rCLmil; R(2)=0.809, P<0.0001). Significant correlations were observed between CLcr and the plasma concentration during the continuous infusion. This correlation was expressed as the equation Y=51.1 x (BW/X)+28.2 (X; CLcr, Y; plasma concentration; BW, body weight; R(2)=0.695, P<0.01). CONCLUSION: The pCmil exhibited stability 6 h or later after the continuous infusion of milrinone 0.2 microg/kg/min. The pCmil can be estimated by the value of CLcr and BW.