75 CONCENTRATIONS OF SODIUM 3Α, 7Α--DIHYDROXY-12- OXO 5Β CHOLANATE IN BIOLOGICAL MATERIAL AFTER ITS INTRAVENOUS AND INTRANASAL APPLICATION Snežana Stević 1, Momir Mikov 2, Zorica Stanojević-Ristić 1, Julijana Rašić 1, Leonida Vitković 3 1 Institute for Pharmacology&Toxicology, Medical Faculty Priština- Kosovska Mitrovica, Serbia 2 Department of Pharmacology, Toxicology&Clinical Pharmacology, Medical Faculty Novi Sad, Serbia 3 Institute for Histolog&Embryology, Medical Faculty Priština- Kosovska Mitrovica, Serbia Newly synthetized derivative of bile acid, sodium salt of 3α, 7α-dihydroxy-12-oxo 5β cholanic acid (monoketo- cholanate) expressed a good characteristic as intranasal transport enhancer of xenobiotics.The aim of our sudy was to explore if it has an influence on bile metabolism and to measure its concentration in blood and bile after intravenous and intranasal administration. The experiment was performed in vivo on adult male Wistar rats. The determination of monoketocholanate (MKCh) in rats blood and bile, was carried out by high-performance liquid chromatography (HPLC), on an HP ODS2 column, using methanol/acetonitrile/acetate buffer as mobile phase. Absorbances were measured at 210 nm.Blood samples were taken from the prepared right axillary artery in 0, 1, 5, 10, 20, 30, 60, 90, 120 and 180 minutes from the beginning of the experiment. Bile was collected in a half an hour intervals,during the three hour period. The re- sults showed that MKCh changed the amount of excreted bile depending on the way of application. Intranasal appli- cation increased the bile volume and the MKCh concentration, both in blood and bile compared to the intravenous ap- plication (p<0.05). Distributionm of MKCh through animal organism depends on the way of application of the substance, which probably determines its caracterisation as the transport promotor of applied xenobiotics. HPLC has proved as aa relatively simple, fast and effective method for the determination of synthetic bile acid,MKCh in these biological ma- terials. key words: bile acids and salts, HPLC method, intranasal and intravenous administration, rats INTRODUCTION Bile acids and their salts have found many applica- tions in medicine, agriculture and pharmacy [1, 2, 3]. They are very attractive for substance transport re- searches, according to their chemical properties and de- tergent-like action [4]. Some scientists have reported that bile acids can be used in the monitoring of the phy- logenetic origin of vertebrates [5]. As far as chemical structure is concerned, keto (oxo) derivatives of natural bile acids have been detected as metabolites, named "tertiary bile acids". As is it known, the hydroxy deriva- tive of cholanoic acid is found only in human bile and some amounts of cholanoic acid metabolite is found only in human feces [6]. The main intermediates in the proc- ess of reduction of cholic to chenodeoxycholic acid are 3฀,7฀-dihydroxy-12-keto-5฀ cholanoic acid and its esters [7]. Monoketocholanate, its sodium salt, has been syn- thesized from 3฀,7฀-trihydroxy-12-keto-5฀ cholanoic acid [8]. This salt appeared to be an effective promoter of in- tranasal resorption of insulin [9, 10, 11], as well as sali- cylates or morphine transport through the brain endo- thelial cells [12, 13]. The aim of this work was to examine the possible in- fluence of MKCh on bile secretion by measuring the amount of excreted bile. Another challenge was to de- termine, for the first time, the MKCh concentration in blood and bile, after intravenous and intranasal applica- tions of MKCh in experimental rats.. STUDY OBJECTIVE The aim of this work was to examine the possible in- fluence of MKCh on bile secretion by measuring the amount of excreted bile. Another challenge was to de- termine, for the first time, the MKCh concentration in ORIGINAL ARTICLES AUTHORS SUMMARY CORRESPONDENT SNEŽANA STEVIĆ 1Institute for Pharmacology&Toxicology, Medical Faculty Priština- Kosovska Mitrovica, Serbia  s.hadzistevic@med.pr.ac.rs doi:10.5937/pramed1802075S