目的:建立大鼠肠灌流液中福辛普利钠的HPLC测定方法,研究福辛普利钠在大鼠小肠的吸收性质。方法:采用HPLC法测定肠灌流液中福辛普利钠的浓度,考察大鼠小肠单向灌流试验中不同肠段、灌流液pH值和二肽甘氨酰肌氨酸(Gly-Sar)浓度对药物肠道渗透性的影响。结果:HPLC方法的专属性和重现性均符合生物样品测定要求,内源性物质不干扰测定。福辛普利钠在大鼠不同肠段的有效渗透系数大小依次为十二指肠〉空肠〉回肠;药物在三肠段的吸收随着灌流液pH值的降低呈增加趋势;此外,低浓度Gly-Sar可促进福辛普利钠的小肠吸收。但浓度较高时则有一定抑制作用。结论:本文建立的HPLC方法简便、灵敏、精密度好,可用于福辛普利钠肠道吸收的研究;影响Peptl活性的因素可改变福辛普利钠的肠道吸收。
OBJECTIVE To establish an HPLC method for determining concentrations of fosinopril sodium in the rat intesti nal perfusate and study the absorption of fosinopril sodium in rat intestine. METHODS HPLC was used to determine the con- centration of fosinopril sodium. In situ single-pass intestinal perfusion was employed to investigate the effects of different intes tine segments,different pH of perfusate and different concentrations of Gly-Sar on the permeability of fosinopril sodium in rat intestine. RESULTS An HPLC method was developed and endogenous substances did not interfere with the assay. Fosinopril sodium was mainly absorbed in the upper small intestine (duodenum and jejunum), and the lower pH of perfusate enhanced the intestinal absorption of fosinopril sodium in different segments of rat intestine. The lower concentration Gly Sar could increase the absorption of fosinopril sodium,however the high concentration reduced the absorption. CONCLUSION The HPLC method used in the present study is simple, sensitive,accurate and can be used to study the absorption of fosinopril sodium in rat intes- tine. The factors which affected the active of Peptl could change the intestinal absorption of fosinopril sodium.