A simple improved method for the measurement of cyclosporin by liquid-liquid extraction of whole blood and isocratic HPLC

Autor: Stephen J Fletcher, Robby A Bacchus
Rok vydání: 1988
Předmět:
Zdroj: Annals of clinical biochemistry. 25
ISSN: 0004-5632
Popis: SUMMARY. The current HPLC methods of cyclosporin measurement have been reviewed and all aspects assessed. A simple isocratic C-18 reverse phase HPLC method with improved efficiency is described for the routine measurement of cyclosporin in whole blood. An alkaline ether extraction is followed by an acid wash, solvent evaporation and two hexane washes of the reconstituted extract. The turn-round time for a single sample is 1 h. Daily batches of up to 40 patient samples can be easily measured with this method. The results are compared with those from the Sandoz radioimmunoassay (RIA) method. Cyclosporin (Cs) is widely used as an effective and potent immunosuppressant in organ transplantation. I At present the benefits to be gained from its use in preventing graft rejection far outweigh the risks of nephrotoxicity. 2 Cyclosporin has a narrow therapeutic index. Wide variability in its pharmacokinetics ne­ cessitates individualised dosage adjustment." This should be based on the measured level in blood, plasma or serum. The pre-dose ther­ apeutic range is dependent on the method of measurement, type of sample used. organ transplanted, dosing interval and time since operation." Levels below the appropriate range are associated with an enhanced risk of graft rejection, or graft-versus-host disease in bone marrow transplants. Levels above the range are associated with nephrotoxicity.5. 6 Cyclosporin levels in blood. serum or plasma are most commonly measured by RIA. This method has the disadvantages of a 48 h turn­ around time and of being non-specific. The antibody cross-reacts with many cyclosporin metabolites,7-12 which have only low immuno­ suppressive activities and may not contribute to the clinical effect. I3-15 There is evidence that
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