Validation of a high-performance liquid chromatography assay for urinary nedocromil sodium following oral and inhaled administration.

The validation of a solid-phase extraction and an ion pair high-performance liquid chromatographic assay for the determination of nedocromil sodium (NCS) in urine samples following oral and inhaled administration to healthy volunteers is described. NCS and its internal standard sodium cromoglycate (SCG) were extracted from urine samples using solid-phase extraction and then quantified using high-performance liquid chromatography (HPLC). A 25-cm C8 Spherisorb 5 microm stationary phase with a mobile phase containing a long alkyl chain ion-pair reagent (methanol-0.045 M phosphate buffer-0.05 M dodecyl triethyl ammonium phosphate; 550:447.6:2.4, v/v) was used. The mean (S.D.) intra-day accuracy and precision of the HPLC assay was 99.9 (1.6) and 7.05 (4.9)%, respectively. These values for the inter-day data were 102.4 (4.07) and 10.5 (2.7)%, respectively, over the concentration range investigated. The method described permits the detection of NCS in human urine at concentrations as low as 0.04 microg ml(-1) where the signal-to-noise ratio is greater than 3:1. In 10 healthy volunteers a significantly greater amount of NCS was excreted in the urine following inhalation than after oral dosing (p<0.001). The mean (S.D.) amount of NCS renally excreted at 0.5, 1.0 and 24 h following inhalation of four 2-mg doses of NCS from a metered dose inhaler (MDI) was 0.513 (0.24), 1.163 (0.49) and 4.00 (1.73)% of the nominal dose. Similar values after oral administration of 8 mg of NCS were 0.026 (0.03), 0.079 (0.06) and 0.930 (0.74)%, respectively.