Determination of sodium cromoglycate in human plasma by liquid chromatography with tandem mass

Abstract

A sensitive and selective liquid chromatography–tandem mass spectrometric (LC–MS/MS) method was developed and validated for the determination of sodium cromoglycate (SCG) in human plasma after a nasal dose of 10.4 mg sodium cromoglycate nasal spray, using pravastatin sodium as the internal standard. The method was validated over a linear range of 0.300–20.0 ng/mL. SCG and I.S. were extracted from 1.0 mL of heparinized plasma by C₁₈ solid‐phase extraction cartridges using methanol as eluting solvent. The dried residue was reconstituted with 100 µL of mobile phase, and 10 µL was injected onto the LC–MS/MS system. Chromatographic separation was achieved on a C₁₈ column (250 × 4.6 mm i.d., 5 µm particle size) with a mobile phase of methanol–acetonitrile–water (containing 2 mmol/L ammonium acetate; 42.5:42.5:15, v/v/v) at a flow rate of 0.4 mL/min. The analytes were detected with a triple quad LC‐MS/MS using ESI with positive ionization. Ions monitored in the multiple reaction monitoring mode were m/z 469.0 (precursor ion) to m/z 245.0 (product ion) for SCG and m/z 447.2 (precursor ion) to m/z327.1 (product ion) for pravastatin sodium (internal standard) The average recovery of SCG from human plasma was 94.88% and the lower limit of quantitation was 0.3 ng/mL. Results from a 3‐day validation study demonstrated excellent precision and accuracy across the calibration range of 0.3–20 ng/mL. The method was successfully applied to the pharmacokinetic study of SCG in healthy Chinese volunteers. Copyright © 2008 John Wiley & Sons, Ltd.