Sensitive and specific quantification of sirolimus (rapamycin) and its metabolites in blood of kidney graft recipients by HPLC/electrospray- mass spectrometry

Sirolimus (rapamycin) has a macrolide structure and is under clinical investigation as an immunosuppressant after organ transplantation. An HPLC/mass spectrometry assay to quantify sirolimus in blood was developed. 28-O-Acetyl sirolimus was used as internal standard. Blood samples were extracted wit...

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Bibliographic Details
Published in:Clinical chemistry (Baltimore, Md.) Md.), 1996-09, Vol.42 (9), p.1417-1425
Main Authors: Streit, F, Christians, U, Schiebel, HM, Napoli, KL, Ernst, L, Linck, A, Kahan, BD, Sewing, KF
Format: Article
Language:English
Subjects:
Acetic Anhydrides
Analysis
Biological and medical sciences
Chromatography, High Pressure Liquid - methods
Drug Monitoring - methods
General pharmacology
Humans
Immunosuppressive Agents - blood
Kidney Transplantation
Mass Spectrometry - methods
Medical sciences
Molecular Structure
Pharmacology. Drug treatments
Polyenes - blood
Sensitivity and Specificity
Sirolimus
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Summary:Sirolimus (rapamycin) has a macrolide structure and is under clinical investigation as an immunosuppressant after organ transplantation. An HPLC/mass spectrometry assay to quantify sirolimus in blood was developed. 28-O-Acetyl sirolimus was used as internal standard. Blood samples were extracted with C18 columns. The extracts were injected into an HPLC system and isocratically eluted with methanol/1% formic acid (90/10 by vol) from a 150 X 4 mm C18 analytical column. The HPLC system was connected to a triple-stage quadrupole mass spectrometer with an electrospray interface and positive ions were detected. The limit of quantification in 1 mL of blood was 0.25 microgram/L and the calibration curve in blood was linear up to 250 microgram/L. The recovery from blood was 88 +/- 26% and interassay variation at 1 microgram/L was 19% and at 15 microgram/L 9.3%. Hydroxy, dihydroxy, demethyl, and didemethyl sirolimus as well as sirolimus were detected in blood of kidney graft patients.
ISSN:0009-9147
1530-8561
DOI:10.1093/clinchem/42.9.1417