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Biomedical subjects

R K Brown

Publications and source records attributed to R K Brown.

71 records · Page 4Linked to original sources

A method for the measurement of L-phenylalanine mustard in the mouse and dog by high-pressure liquid chromatography.

The distribution of L-phenylalanine mustard (L-PAM) was studied in dogs and mice by high-pressure liquid chromatography. Separation of L-PAM from its products of hydrolysis was accomplished with a mu-Bondapak C18 column, a solvent system composed of 2-methoxyethanol/0.1% acetic acid, and solvent programming with a step gradient. Complete separation was effected in less than 15 min. The half-life for disappearance of L-PAM from mouse blood was 41 min, whereas that from dog blood was 29 min. The monohydroxy derivative of L-PAM, L-MOH, disappeared from dog serum with a half-life of 32 min. L-MOH was not detectable in mouse tissue other than blood at times greater than 15 min after injection. In the dog at 4 hr after injection, the tissue/serum concentration ratios were greater than 1 for liver, spleen, intestine, skeletal muscle, urinary bladder and gallbladder. The concentration of L-PAM in the bile was approximately 500 times higher than that in serum.

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Distribution and elimination of melphalan in rats and monkeys and distribution in tumors of mice bearing L1210 or P388 leukemias sensitive and resistant to this agent.

Following iv injection, melphalan was eliminated monophasically from rat serum (half-life = 0.87 hour) and monkey serum (half-life = 1.9 hours) and in rat bile (half-life = 2.4 hours) and monkey urine (half-life = 1.3 hours). In rat bile and monkey urine, 2% and 20% of the dose, respectively, was excreted in 12 hours as unchanged melphalan. At each time of tissue assay (0.5-4 hours after injection), rat spleen contained less melphalan than serum, liver, or kidneys. The kidneys and bile of monkeys contained more melphalan that serum, liver, or spleen. Only a small amount of radioactivity from labeled melphalan appeared in the feces of monkeys. Melphalan reached higher concentrations in implants of P388 and L1210 leukemia cells sensitive to melphalan than in cell lines resistant to this drug. Furthermore, the amounts of radioactivity bound to macromolecules of the sensitive tumors were higher.

Animals↗