Aswania O A, Corlett S A, Chrystyn H
School of Pharmacy, University of Bradford, UK.
J Chromatogr B Biomed Sci Appl. 1998 Nov 6;718(2):290-5. doi: 10.1016/s0378-4347(98)00379-x.
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.
本文描述了一种用于测定健康志愿者口服和吸入给药后尿液样本中奈多罗米钠（NCS）的固相萃取和离子对高效液相色谱分析方法的验证。使用固相萃取从尿液样本中提取NCS及其内标色甘酸钠（SCG），然后用高效液相色谱（HPLC）进行定量分析。采用一根25 cm的C8 Spherisorb 5微米固定相，流动相包含一种长链烷基离子对试剂（甲醇-0.045 M磷酸盐缓冲液-0.05 M十二烷基三乙铵磷酸盐；550:447.6:2.4，v/v）。HPLC分析的日内准确度和精密度均值（标准差）分别为99.9（1.6）%和7.05（4.9）%。在所研究的浓度范围内，日间数据的相应值分别为102.4（4.07）%和10.5（2.7）%。所述方法能够检测人尿液中低至0.04微克/毫升的NCS，此时信噪比大于3:1。在10名健康志愿者中，吸入后尿液中排出的NCS量显著多于口服给药后（p<0.001）。从定量吸入器（MDI）吸入四剂2毫克NCS后，在0.5、1.0和24小时经肾脏排出的NCS平均（标准差）量分别为标称剂量的0.513（0.24）%、1.163（0.49）%和4.00（1.73）%。口服8毫克NCS后的相似值分别为0.026（0.03）%、0.079（0.06）%和0.930（0.74）%。
