Gas chromatographic assay for the new antitumor agent sulfamic acid diester (NSC 329680) and its stability in buffer, blood and plasma.
A sensitive gas chromatographic assay with electron-capture detection has been developed for sulfamic acid diester (sulfamic acid 1,7-heptanediyl ester, NSC 329680) based on its conversion to 1,7-diiodoheptane in the presence of excess sodium iodide. The assay is linear up to 1 microgram/ml sulfamic acid diester and has a lower limit of detection of 25 ng/ml from 0.5 ml plasma. The coefficient of variation of the assay is 6.4% at 1 microgram/ml and 8.0% at 100 ng/ml. Sulfamic acid diester is relatively stable in 0.9% sodium chloride and 0.1 M sodium phosphate buffers, pH 7.0-9.0, with half-lives greater than 38 h. The major breakdown product of sulfamic acid diester is sulfamic acid 1,7-heptane-monoyl ester. When added to whole blood sulfamic acid diester shows concentration-dependent breakdown. At 50 and 100 micrograms/ml sulfamic acid diester, the half-time in whole blood is 6.9 h and 65% of the drug is sequestered by the blood cells. At 10 micrograms/ml sulfamic acid diester in blood, there is no detectable breakdown of the drug over 24 h and all of the drug is sequestered by the blood cells. Protein binding of sulfamic acid diester in human plasma is 82% at 10 micrograms/ml and 68% at 100 micrograms/ml.
Brodfuehrer
J I
JI
Department of Pharmacology, Mayo Clinic & Foundation, Rochester, MN 55905.
Powis
G
G
D000970:Antineoplastic Agents / Q000032:analysis* / Q000097:blood / Q000652:urine; D001798:Blood Proteins / Q000032:analysis; D002849:Chromatography, Gas; D004912:Erythrocytes / Q000032:analysis; D006801:Humans; D013058:Mass Spectrometry; D013451:Sulfonic Acids / Q000032:analysis* / Q000097:blood / Q000652:urine
D000970:Antineoplastic Agents; D001798:Blood Proteins; D013451:Sulfonic Acids; C052475:hepsulfam