Specific and sensitive measurement of FK506 and its metabolites in blood and urine of liver-graft recipients.
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.
Christians
U
U
Institute für Allgemeine Pharmakologie, Medizinische Hochschule Hannover, FRG.
Braun
F
F
Schmidt
M
M
Kosian
N
N
Schiebel
H M
HM
Ernst
L
L
Winkler
M
M
Kruse
C
C
Linck
A
A
Sewing
K F
KF
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
D016559:Tacrolimus