Determination of plasma azathioprine and 6-mercaptopurine in patients with rheumatoid arthritis treated with oral azathioprine.
Two specific high-performance liquid chromatography methods for determining plasma concentrations of azathioprine and 6-mercaptopurine after oral administration of azathioprine are presented. It was shown that azathioprine is unstable in the blood samples unless immediately cooled in ice water. The 2-amino analog, guaneran, was used as internal standard for azathioprine, which was extracted from plasma with ethylacetate. A Nucleosil C18 column was used for the separation. The detection limit was 6 nM. For quantification of 6-mercaptopurine, 6-thioguanine was used as internal standard. Plasma was deproteinized with HClO4 and the sample was purified on mercurial cellulose. A Beckman ODS column was used and the detection limit was 5 nM. Pharmacokinetic data from two patients are presented. Unchanged azathioprine was seen until 6 h after an oral dose of 32 mg/m2.
Department of Medicine, Karolinska Institute, Huddinge Hospital, Sweden.
J
J
Liliemark
B
B
Pettersson
P
P
Lafolie
T
T
Zweig
C
C
Peterson
D000284:Administration, Oral; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000032:analysis; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy; D001379:Azathioprine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000032:analysis / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002110:Caffeine / Q000032:analysis; D004355:Drug Stability; D005260:Female; D006801:Humans; D015122:Mercaptopurine / Q000097:blood* / Q000493:pharmacokinetics; D008875:Middle Aged
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002110:Caffeine; C060146:thiamiprine; D015122:Mercaptopurine; D001379:Azathioprine