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D C Chatterji

Publications and source records attributed to D C Chatterji.

31 records · Page 2Linked to original sources
PubMed1979

Formulation and evaluation of ethiodized oil emulsion for intravenous hepatography.

A study was conducted to prepare and evaluate an ethiodized oil emulsion for intravenous administration that would selectively opacify the liver. Several formulations with differing globule size were prepared and compared for their in vivo activity (degree of liver opacification obtained) and stability. Results of studies conducted in rabbits and monkeys revealed that the oil globules that concentrate most in liver were 2.0--3.0 micrometer in diameter. The formulation of choice was stable for 6 months at refrigeration temperature (2--6 degree). In monkeys, this formulation produced an improved diagnostic image of the liver using computerized tomography at a dose of 0.2 ml/kg. The potential use of such emulsions in diagnostic radiology is briefly discussed.

Animals↗
PubMed1979

Stabilization of 5-azacytidine by nucleophilic addition of bisulfite ion.

5-Azacytidine (I) stability was increased approximately 10-fold over its stability in water or lactated Ringer injection by the addition of excess sodium bisulfite and the maintenance of pH approximately 2.5. The increased stability in the presence of bisulfite at pH 2.5 was attributed to the addition of bisulfite across the 5-6 protonated imine bond of I, which prevented the hydrolytic attack on this labile double bond. However, above pH 4, bisulfite increased I degradation. At higher pH, the compound was no longer protonated and bisulfite did not form the stable addition product. The addition compound quickly decomposed above pH 6 to give back the parent compound and, thus, acted as a I prodrug. The intact drug remaining was assayed by high-pressure liquid chromatography (HPLC), and the reversibility of the bisulfite-I addition product above pH 6 was demonstrated by UV spectrophotometry and HPLC. The potential utility of the bisulfite-I addition product as a I prodrug in parenteral and possible oral dosage forms is discussed.

Azacitidine↗
PubMed1979

Development and experimental evaluation of a contrast medium for computed tomographic examination of the liver and spleen.

A lipoid based contrast material containing 53% of ethiodized oil in emulsion form was developed for computed tomography (CT) of the liver and spleen and tested in rabbits and monkeys. An intravenous dose of 0.2 ml/kg selectively opacified the liver and spleen, resulting in an average increase of 23 EMI units (500 scales) in the attenuation of the liver and a higher increase in the attenuation of the spleen. When injected into rhesus monkeys with carcinogen induced hepatomas there was a significant improvement in the visualization of the tumor, and small lesions, undetectable on the preliminary CT scan, became visible. Toxicity studies are in progress.

Animals↗
PubMed1978

Thermal and photolytic decomposition of methotrexate in aqueous solutions.

The chemical kinetics of thermal and photolytic degradation of methotrexate in aqueous solutions were studied. At above pH 7 and 85 degrees, methotrexate hydrolyzed to yield mainly N10-Methylpteroylglutamic acid. The hydrolysis rate followed first-order kinetics with respect to methotrexate concentration and increases rapidly above pH 9. When methotrexate solutions were kept under laboratory fluorescent light, the major degradation products were 2,4-diamino-6-pteridinecarbaldehyde, 2,4-diamino-6-pteridinecarboxylic acid, and p-aminobenzoylglutamic acid. The photolytic reaction followed zero-order kinetics with respect to methotrexate concentration and was catalyzed by bicarbonate ion. Evidence is presented for a proposed sequential cleavage of methotrexate by a free radical mechanism for the photolysis. Commercial parenteral methotrexate was found to be quite stable as marked when stored in the original vial at room temperature.

Chromatography, High Pressure Liquid↗
PubMed1978

Identification and quantitation of impurities in methotrexate.

The impurities in bulk, commercial, and investigational methotrexate samples were chromatographically separated by gradient elution from a diethylaminoethylcellulose column. Besides the already known impurities in the bulk and commercial samples, two other impurities, 4-amino-N10-methylpteroyl-N-methylglutamine and 2,4-di-amino-N10-methylpteramide, were identified. A new batch of methotrexate, synthesized for the National Cancer Institute for investigational use only, showed a different spectrum of impurities. The purity of all methotrexate samples studied was about 80% calculated on an anhydrous basis.

Chemical Phenomena↗
PubMed1978

Mechanism of hydrolysis of halogenated nitrosoureas.

The hydrolysis kinetics of halogenated nitrosoureas were investigated using chlorozotocin as a model. Evidence is presented to show that the hydrolytic reaction of halogenated nitrosoureas between pH 3 and 8 is a summation of spontaneous water and hydroxide-ion-catalyzed reactions; the later reaction is the sum of two parallel reactions. The relative contribuiton of each reaction changes with pH and results in different product distributions. Dianionic phosphate (HPO42-) increased the amount of free chloride-ion production without significantly altering the hydrolysis rate. A mechanism is proposed to explain this behavior. The role of hydrolytic decomposition products produced at physiological pH on the biological activity of nitrosoureas is discussed.

Chlorides↗
PubMed1977

High-pressure liquid chromatographic analysis of methotrexate in presence of its degradation products.

Two high-pressure liquid chromatographic methods are described for the quantitative determination of methotrexate in the presence of its contaminants and degradation products. Method 1 takes less than 15 min and is recommended for routine assays of methotrexate in commercial products. Method 2 takes about 35 min and is the method of choice to detect and quantitate large amounts of degradation products. Quantitation to a level of 1 microgram of methotrexate/ml is feasible by these methods and thus provides potential applicability for the analysis of methotrexate in biological fluids.

Chromatography, DEAE-Cellulose↗
PubMedDate not supplied

Systemic bioavailability and pharmacokinetics of methylprednisolone in patients with rheumatoid arthritis following 'high-dose' pulse administration.

The absolute and relative bioavailability of two methylprednisolone formulations (capsules and suspension) was determined along with its pharmacokinetics in four arthritic female patients, following an unconventional high-dose pulse of 1 g. Plasma concentrations of the drug were measured by a sensitive and specific high-performance liquid chromatographic (HPLC) procedure. The disposition of methylprednisolone from plasma following intravenous (i.v.) infusion of its succinate ester appeared monoexponential with a mean half-life of 2.4 h and an apparent volume of distribution (Vd) of 50 l (0.87 l/kg). The total body clearance (Cl) averaged 15.12 l/h. Absolute bioavailability was assessed by comparing the areas under the plasma concentration time curves (normalized to dose) following oral administration of capsule or suspension with those of intravenous administration. No significant difference (p greater than 0.2) was observed when systemic availability (f, expressed in per cent) following administration of drug in capsule (f = 49.35 per cent) was compared with that obtained following the administration of drug in a suspension (f = 58.26 per cent). The difference in the observed and predicted f may be due to incomplete absorption, hepatic and/or extrahepatic metabolism of methylprednisolone. Subjective evaluation showed no side effects of this high-dose pulse therapy in any of the patients.

Administration, Oral↗
PubMedDate not supplied

Pharmacokinetics of 6-mercaptopurine (6MP) in the monkey. I. Disposition from plasma and cerebrospinal fluid following iv bolus.

The disposition profile of 6-mercaptopurine (6MP) was studied from plasma and cerebrospinal fluid (CSF) in the rhesus monkey following a single iv bolus dose (4 mg/kg). A new, sensitive, and specific high performance liquid chromatography procedure has been employed for drug quantitation in biological fluids. An equation consisting of three exponential terms was simultaneously fitted to the 6MP plasma and CSF concentration vs. time data using the SAAM 27 digital computer program. 6MP in plasma and CSF had a mean half-life (t1/2, lambda z) of 2.9 hr and an apparent volume of distribution (Vd, lambda z) of 3.00 liter/kg. Estimates of total body clearance average 0.731 +/- 0.412 liter/hr/kg and ranged between 0.446 and .1204 liter/hr/kg. In the postdistributive phase, the decline of 6MP concentration from the CSF paralleled plasma. The t1/2, lambda z obtained by fitting Ccsf vs. t data separately was not significantly different (p greater than 0.2) than the one obtained above in a simultaneous fitting of the data. Therefore, it appears that the unbound 6MP concentration in plasma may be the driving force in the diffusion of the drug into CSF. Comparison of experimental CSF/plasma ratio of 6MP with the theoretical values obtained using the pH-partition hypothesis is also discussed.

Animals↗