SEPARATION AND IDENTIFICATION OF IMPURITIES IN PARENTERAL METHOTREXATE DOSAGE FORMS

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  • 1 January 1978
    • journal article
    • research article
    • Vol. 62  (1) , 13-18
Abstract
Lots (11) of parenteral methotrexate (MTX [antineoplastic agent]) dosage forms from 2 manufacturers were analyzed and were 93.4% .+-. 2.1% (SD) pure by a new procedure employing a DEAE-cellulose column adapted for high performance liquid chromatography instrumentation. In addition to 4-amino-10-methylpteroic acid and N10-methylpteroylglutamic acid, which were previously identified contaminants, and benzyl alcohol which was added as a preservative, 2,4-diamino-6-methylpteridine, 2,4-diamino-6-bromomethylpteridine and p-methylaminobenzoic acid were also isolated and identified. Another impurity was tentatively identified as 4-amino-10-methylpteroic acid amide. The individual impurities vary from 0.1-4.8% of the UV absorbing material which elutes from the column. Additional impurities were detected by gas chromatography-mass spectrometry. Since high-dose therapy may involve the administration of up to 20 g of MTX/day, the effect of the impurities present in these dosage forms on the course of the patient''s therapy should be determined.