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- W2364457978 abstract "In a previous communication,we have reported the physiological disposition of N-C~(14)-formylsarcolysine.In as much as the tracer technic does not distinguish the unchanged drug from its metabolite(s),a highly specific method is developed for the determination of N-formylsarcolysine in biological samples. One ml of sample (whole blood,tissue homogenate (1:5),urine (1:1),bile and feces (1:10)) was pipetted into a centrifuge tube containing 20-40 mg of sodium bicarbonate and well shaken until dissolved.To the alkaline sample,10 ml of absolute alcohol was added to precipitate protein.The protein-free supernatant was evaporated to dryness under reduced pressure.The residue was dissolved in 5 ml of 0.1 M acetate buffer (pH 3.6) and extracted three times with 5 ml volumes of ethyl acetate.The pooled extract was again evaporated to dryness.The residue was dissolved in 5 ml of absolute alcohol and the light absorptions measured at 240,258 and 280 mμ.Since the absorption curve obtained from biological specimens is the additive effect of the absorption due to the blank specimen (which is essentially a straight line between 240 and 280 mμ,fig.1,Ⅲ) plus the actual N-formylsarcolysine curve,it is evident that the peak absorption at 258 mμ cannot be used as a measurement of drug concentra- tion without subtracting an unknown fraction contributed by the blank specimen.Based on the absorption spectrum of N-formylsarcolysine (fig.1,I),points A,B and C represent the optical densities at 258 (maximum absorption),240 and 280 mμ res- pectively.When a line was drawn from A perpendicular to the abscissa and crosses BC at D,the distance between A and D was found to be proportional to the quantity of N-formylsarcolysine in the sample.Interference by blank materials may thus be elimi- nated.The magnitude of D may also be calculated according to the equation: D=0.55B+0.45C. This method was shown to be very sensitive and highly specific. Five hours after an oral dose of N-formylsarcolysine (200 mg/kg) to normal rats, about 7.9% of the dose could be recovered from the gastrointestinal tract as unchanged drug.Since in vitro experiments showed that N-formylsarcolysine was rapidly meta- bolized to compounds not determined by this method,the disappearance of N-formyl- sarcolysine from the gastrointestinal tract does not reflect the actual absorption of the drug. When injected intravenously to rats and rabbits,N-formylsarcolysine disappeared rapidly from the blood with a biological half life of 12-15 minutes.In normal rats, about 23.8% of the administered dose was excreted in the urine in five hours.During the same period,the urinary excretion by rabbits was about 12.5%.In rats with a biliary cannula,as much as 12.4% of an intravenously injected dose could be reco- vered from the bile in five hours. One hour after N-formylsarcolysine (100 mg/kg) was given intravenously to normal rats or rats bearing Yoshida solid carcinoma,appreciable concentration was found in the kidneys,relatively low concentrations were present in the liver,while only trace amounts were present in the tumour and other tissues examined. When a dose of 300 mg of N-formylsarcolysine was given orally to patients suffer- ing from seminoma of the testis,very low concentrations of unchanged drug were found in the blood.About 7.1% of the administered dose was excreted in the urine. The hydroxy form of N-formylsarcolysine was shown to be the main metabolite in rats as well as in patients." @default.
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- W2364457978 date "1965-03-01" @default.
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- W2364457978 title "[THE METABOLIC FATE OF N-FORMYLSARCOLYSINE AND A METHOD FOR ITS DETERMINATION IN BIOLOGICAL MATERIALS]." @default.
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