【摘要】 目的采用高效液相色谱法（HPLC）检测患者羟苯磺酸钙常规剂量用药后的稳态血药浓度,分析该浓度与患者肾小球滤过率（eGFR）及药物所致肌酐干扰的相关性,为肾功能不全患者调整羟苯磺酸钙用药剂量提供依据。方法①选择并优化检测血清羟苯磺酸钙浓度的HPLC方法,并进行方法学评价;②选择2016年5～10月间黄石市第二医院收治20例肾功能不全和10例非肾功能不全羟苯磺酸钙（剂量为1.5 g/d,Tid）用药患者,采集羟苯磺酸钙服药5天后清晨空腹静脉血,HPLC法检测血清羟苯磺酸钙浓度;③比较肾功能不全组、非肾功能不全组稳态血清羟苯磺酸钙浓度差异,分析肾功能不全组稳态血清羟苯磺酸钙浓度与eGFR及肌氨酸氧化酶法肌酐干扰值相关性。结果①HPLC方法学评价结果:方法专属性色谱图表明羟苯磺酸钙、对氨基苯甲酸内标保留时间分别为:6.9和8.0 min,血清内源性物质不干扰羟苯磺酸钙测定;羟苯磺酸钙及对氨基苯甲酸内标平均萃取回收率分别为:75.5%和94.5%,线性范围:1.90～189.60 mg/L（r²=0.999 1,P<0.01）,检测低限:0.452 mg/L,平均加标回收率98.9%（95.6%～103.6%）,18.96,94.80和189.60 mg/L三种浓度测试样品日内CV分别为4.8%,4.5%和4.1%,日间CV分别为6.3%,6.1%和5.4%。②稳态血清羟苯磺酸钙检测结果:肾功能不全组高于非肾功能不全组（146.10±91.86 vs 16.81±2.48 mg/L）,差异有统计学意义（Z=-4.400,P<0.05）。③肾功能不全组稳态血清羟苯磺酸钙浓度与eGFR呈负相关（r=-0.790,P=0.000）,回归方程为Y=6 080.61X^-1.692（r²=0.975 3,F=710.882,P=0.001）;肾功能不全组肌氨酸氧化酶法肌酐干扰值与稳态血清羟苯磺酸钙浓度呈正相关（r=0.816,P=0.000）,回归方程为Y=0.002 7X 2+0.343 5X+22.935（r²=0.987 5,F=671.064,P=0.000）。结论肾功能不全患者常规剂量服用羟苯磺酸钙后出现与eGFR呈负相关的药物蓄积,建议肾功能不全患者使用羟苯磺酸钙应依据eGFR降低用药剂量。更多还原

【Abstract】 Objective The steady-state plasma concentration of calcium dobesilate was measured by HPLC and its correlation with eGFR and drug-induced creatinine interference was analyzed, and provide the basis for adjusting the dosage of calcium dobesilate in patients with renal insufficiency.Methods ①Selected and optimized an HPLC method for detercting the concentration of calcium dobesilate in serum,and corried out methodological evaluation.②Selected 20 cases of renal insufficiency and 10 cases of non-renal insufficiency patients in the treatment of calcium dobesilate patients（in the dose of 1.5 g/d,Tid） from May to October of 2016.Collected fasting venous blood in the morning after inhalation of calcium dobesilate for 5 days,and the concentration of calcium dobesilate in serum was detected by HPLC.③Compared the difference of stable serum calcium dobesilate concentration between renal insufficiency group and non-renal insufficiency group,analysis of correlation of serum calcium dobesilate concentration and eGFR and creatine oxidase-induced creatinine interference in patients with functional insufficiency.Results ①Optimized HPLC methodological evaluation results:the retention time of calcium dobesilate and aminobenzoic acid were about 6.9 min and 8.0 min,respectively.The results showed that the serum endogenous substances did not interfere with the effect of calcium dobesilate.The recoveries of calcium dobesilate and internal standard p-aminobenzoic acid were 75.5% and 94.5%,respectively.The linear range was 1.90～189.60 mg/L（r²=0.999 1,P<0.05）,and detection limit:0.452 mg/L.The average recoveries were 98.9%（95.6%～103.6%）,and the CVs of three concentrations of test samples of 18.96,94.80 and 189.60 mg/L were 4.8%,4.5% and 4.1% respectively,and daytime CV were:6.3%,6.1% and 5.4% respectively.②Steady-state serum calcium dobesilate test results:calcium dobesilate has a significant difference between the two groups 14.61±91.86 vs 16.81±2.48 mg/L,the difference was statistically significant（Z=-4.400,P<0.05）.③Serum calcium dobesilate concentration in patients with renal insufficiency was significantly negatively correlated with eGFR（r=-0.790,P=0.000）.The regression equation was Y=608 0.61X^-1.692（r²=0.975 3,F=710.882,P=0.001）.The concentration of creatinine was significant positive correlation of steady-state serum calcium dobesilate（r=0.816,P=0.000）.The regression equation was Y=0.002 7X²+0.343 5X+22.935（r²=0.987 5,F=671.064,P=0.000）.Conclusion Patients with renal insufficiency had a negative association with eGFR after routine doses of calcium dobesilate.It is recommended that patients with renal insufficiency use calcium dobesilate should be reduced according to eGFR.更多还原