title: Specific and sensitive measurement of FK506 and its metabolites in blood and urine of liver-graft recipients.
abstract: A specific and sensitive assay for quantifying the immunosuppressant FK506 and its metabolites in blood and urine was developed. 32-O-Acetyl FK506 was synthesized and used as internal standard. FK506 and its metabolites were purified from the samples by solid-liquid extraction and were injected into a high-performance liquid chromatographic (HPLC) system linked to a mass spectrometer (MS) by particle-beam interface. The FK506 derivatives were separated from interfering material by use of a 100 x 4 mm C8 analytical column and water/acetonitrile or water/methanol gradient elution; they were detected by negative chemical ionization with methane as reagent gas. The limit of detection was 25 pg in a standard solution, and the limit of quantification in blood was 250 pg (extracted from 1 mL of blood). The CV was 11.3% at 5 ng, and no interferences with other drugs were found.
authors.affiliation: Institute für Allgemeine Pharmakologie, Medizinische Hochschule Hannover, FRG.
authors.forename: U
authors.initials: U
authors.lastname: Christians
authors.forename: F
authors.initials: F
authors.lastname: Braun
authors.forename: M
authors.initials: M
authors.lastname: Schmidt
authors.forename: N
authors.initials: N
authors.lastname: Kosian
authors.forename: H M
authors.initials: HM
authors.lastname: Schiebel
authors.forename: L
authors.initials: L
authors.lastname: Ernst
authors.forename: M
authors.initials: M
authors.lastname: Winkler
authors.forename: C
authors.initials: C
authors.lastname: Kruse
authors.forename: A
authors.initials: A
authors.lastname: Linck
authors.forename: K F
authors.initials: KF
authors.lastname: Sewing
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000706:statistics & numerical data; D006801:Humans; D016031:Liver Transplantation; D013058:Mass Spectrometry; D008832:Microchemistry; D008862:Microsomes, Liver / Q000737:chemistry; D011786:Quality Control; D016559:Tacrolimus / Q000032:analysis* / Q000097:blood / Q000652:urine
chemical_list: D016559:Tacrolimus