title: A new method for determination of both thalidomide enantiomers using HPLC systems.
abstract: Although thalidomide was withdrawn due to teratogenicity and neuropathy, there is now growing clinical interest in this compound because of its immunomodulatory and anti-angiogenic properties. In 1998, thalidomide was approved by the U.S. Food and Drug Administration for the treatment of erythema nodosum leprosum (ENL), an inflammatory complication of Hansen's disease, through a restricted-use program. Thalidomide was approved for the treatment of relapsed or refractory multiple myeloma (MM) as an orphan drug in Japan. Direct deproteinization method was shown to be useful for quantitation of enantioselective thalidomide blood level. Stabilized blood was deproteinized with methanol and 2 M trichloroacetic acid. The supernatant was injected onto reverse-phase column (CHIRALPAK AD-RH). The mobile phase consisted of 10% acetonitrile, 70% methanol and 20% 0.025 m citrate buffer (pH 3.0), and the flow rate was 0.5 ml/min. Wavelength of detection was 220 nm. (-)-(S)-thalidomide and (+)-(R)-thalidomide were separated at 13.5 min and 17.6 min, respectively. The accuracy of this method was almost the same as that of the measurement technique with extraction and concentration. In clinical practice, MM patients usually take many kinds of drugs at the same time. Actually, this patient takes a lot of drugs with thalidomide. However, we found no interference of these drugs and thalidomide on the chromatogram. This simple and reliable HPLC determination method for both enantiomers of thalidomide is thought to be very useful for thalidomide studies.
authors.affiliation: Department of Pharmacy, Sapporo Japan Post Hospital, 5-1, Kawazoe 14-jo 1-chome, Minami-ku, Sapporo 005-8798, Japan.
authors.forename: Kaname
authors.initials: K
authors.lastname: Sembongi
authors.forename: Masanori
authors.initials: M
authors.lastname: Tanaka
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sakurada
authors.forename: Masaki
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Shirou
authors.initials: S
authors.lastname: Itagaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hirano
authors.forename: Ken
authors.initials: K
authors.lastname: Iseki
mesh_terms: D020533:Angiogenesis Inhibitors / Q000097:blood* / Q000737:chemistry / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D006801:Humans; D015394:Molecular Structure; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D013792:Thalidomide / Q000097:blood* / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D020533:Angiogenesis Inhibitors; D013792:Thalidomide