title: The detection of chemical impurities by high pressure liquid chromatography and the genetic activity of medical grades of pyrvinium pamoate in Saccharomyces cerevisiae and Salmonella typhimurium.
abstract: The genetic activity of several medical grades of the anthelmintic drug pyrvinium pamoate, which is a dipyrvinium salt, was studied in a diploid mitotic recombination and gene conversion assay (strain D5 of Saccharomyces cerevisiae), and in several haploid yeast reversion assays (strains XV185-14C, XY718-1A, and 7854-1A). All of the samples were recombinogenic in strain D5 and mutagenic in the haploid strains, however, the degree of genetic activity varied considerably among the medical grades of pyrvinium pamoate that were tested. Similarly, these samples varied in degree of mutagenicity when they were tested in strains TA97, TA98, TA100, and TA102 of Salmonella typhimurium, but some of the medical grades of pyrvinium pamoate were mutagenic both in the presence and in the absence of the metabolic transformation system, whereas other medical grades of the drug required such activation to be mutagenic. In addition, the medical grades and dosage forms of several brands of pyrvinium pamoate were examined for purity by fluorescence high pressure liquid chromatography (HPLC) using a methanol:water (90:10) solvent system. The HPLC data indicate that monopyrvinium salts are the major contaminants in these pharmaceuticals. In general, there is a correlation between the degree of genetic activity and toxicity, and the number and relative quantity of impurities found in each sample.
authors.forename: U G
authors.initials: UG
authors.lastname: Hennig
authors.forename: L G
authors.initials: LG
authors.lastname: Chatten
authors.forename: R A
authors.initials: RA
authors.lastname: Pon
authors.forename: R C
authors.initials: RC
authors.lastname: von Borstel
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000032:analysis / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D004340:Drug Contamination; D066298:In Vitro Techniques; D009152:Mutagenicity Tests; D009153:Mutagens; D011774:Pyrvinium Compounds / Q000032:analysis / Q000633:toxicity*; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics*; D013607:Tablets
chemical_list: D000871:Anthelmintics; D009153:Mutagens; D011774:Pyrvinium Compounds; D013607:Tablets; C024631:pyrvinium