Fluorometric assay using high-pressure liquid chromatography for the microsomal metabolism of certain substituted aliphatics to 1,N6-ethenoadenine-forming metabolites

High-Performance Liquid Chromatographic–Fluorescent Method to Determine Chloroacetaldehyde, a Neurotoxic Metabolite of the Anticancer Drug Ifosfamide, in Plasma and in Liver Microsomal Incubations

“…Potential interfering substances, such as other aldehydes, do not affect CA determination, as evidenced by the low background fluorescent intensity observed in time 0 plasma samples. Of note, CA can also be generated from several common industrial chemicals, including carcinogenic haloaliphatics, such as vinyl chloride and 1,2-dichloroethane (13,14). Other monohaloacetaldehydes, including bromoacetaldehyde, may react with adenosine and form 1-N 6 -ethenoadenosine (14).…”

“…Of note, CA can also be generated from several common industrial chemicals, including carcinogenic haloaliphatics, such as vinyl chloride and 1,2-dichloroethane (13,14). Other monohaloacetaldehydes, including bromoacetaldehyde, may react with adenosine and form 1-N 6 -ethenoadenosine (14). Populations with high exposure to these chemicals may therefore have higher background levels of CA in their plasma, suggesting that the present assay may also be useful for monitoring chemical exposure leading to CA formation in these individuals.…”

“…CA primarily causes tubule toxicity rather than hemorrhagic cystitis, which is caused by acrolein, an IFA metabolite formed during the decomposition of 4-OH-IFA to yield isophosphoramide mustard, the therapeutically active metabolite (12). CA can, however, also bind to DNA (particularly adenine bases) and form etheno adducts (13)(14)(15).…”