title: High-performance liquid chromatographic assay of plasma thalidomide: stabilization of specimens and determination of a tentative therapeutic range for chronic graft-versus-host disease.
abstract: Thalidomide is now widely used to treat chronic graft-versus-host disease, but its use is associated with non-teratogenic side effects such as peripheral neuropathy. To examine the value of monitoring plasma concentrations of the drug in such patients, we have developed a high-performance liquid chromatographic (HPLC) assay. The method uses 0.5 mL plasma, is linear to 10 mg/L and had a detection limit of 0.2 mg/L. Thalidomide in plasma specimens was unstable at physiological pH but could be stabilized for several weeks by simple acidification. We describe a protocol for monitoring patients treated with thalidomide which permits convenient transportation and storage of specimens and report, provisionally, that plasma concentrations in the range 1-7 mg/L are therapeutically effective in chronic graft-versus-host disease without adverse side effects.
authors.affiliation: Department of Haematology, Queen Elizabeth Hospital, Birmingham, UK.
authors.forename: B J
authors.initials: BJ
authors.lastname: Boughton
authors.forename: T M
authors.initials: TM
authors.lastname: Sheehan
authors.forename: J
authors.initials: J
authors.lastname: Wood
authors.forename: D
authors.initials: D
authors.lastname: O'Brien
authors.forename: M
authors.initials: M
authors.lastname: Butler
authors.forename: A
authors.initials: A
authors.lastname: Simpson
authors.forename: K A
authors.initials: KA
authors.lastname: Hale
mesh_terms: D002851:Chromatography, High Pressure Liquid; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D006086:Graft vs Host Disease / Q000188:drug therapy*; D006801:Humans; D016014:Linear Models; D008297:Male; D008991:Monitoring, Physiologic / Q000379:methods*; D013048:Specimen Handling / Q000379:methods*; D013792:Thalidomide / Q000097:blood*
chemical_list: D013792:Thalidomide