High-performance liquid chromatography assay with programmed flow elution for cisatracurium in human plasma: Application to pharmacokinetics in infants and children

• An HPLC-FLD method with programmed flow elution for the quantification of cisatracurium in human plasma was developed and fully validated.
• The programmed flow elution allowed the analysis to be performed within a short time.
• The ternary eluent method employed allowed complete separation of the analytes from the endogenous substances.
• Small volumes of plasma samples were required for sample preparation which was suited to infants and children patients.
• The developed HPLC method was suitable for the pharmacokinetic investigations in infants and children of cisatracurium after intravenous administration.

A high-performance liquid chromatography (HPLC) assay with fluorescence detection (FLD) for quantification of cisatracurium in human plasma was developed and fully validated. Liquid–liquid extraction was employed for sample preparation. The separation was carried out on a C18 column with ternary mobile phase composed of 30 mmol L−1 phosphate buffer (pH 3.0), acetonitrile and methanol (60:35:5, v/v/v). Verapamil was used as the internal standard. The isocratic elution with programmed flow rate was employed by setting at 0.8 mL min−1 from 0 to 3.5 min, 0.5 mL min−1 from 3.5 to 6 min, and 1.0 mL min−1 from 6 to 10 min. The fluorescence detection was performed at 236 nm for excitation and 324 nm for emission. The assay was linear from 50 to 2800 ng mL−1, with a detection limit of 12 ng mL−1. The correlation coefficient (r) for linear regression was 0.9997. The intra-day coefficients of variation (CVs) were less than 2.0%, and the inter-day CVs were less than 4.0%. The mean recoveries were in the range of 92.1–100.4%. The total HPLC run time was less than 10 min. The developed HPLC method was fast, simple, sensitive, accurate and suitable for studying the pharmacokinetics of cisatracurium in infants and children after intravenous administration.