Quantification of cyclosporin A in human cerebrospinal. fluid by liquid chromatography-mass spectrometry using atmospheric pressure chemical ionization

Cyclosporin A (CsA) is widely used as an immunosuppressant in organ transplantation, and the treatment of autommume disorders. This is the first publication describing a rapid, sensitive, and selective liquid chromatography-mass spectrometry (LC-MS) method for analysis of CsA in cerebrospinal fluid (CSF). Chromatographic separation was achieved using a reversed-phase column with a linear gradient mobile phase. A column switching procedure was incorporated to minimize contamination in the ion source of the mass spectrometer. The sample volume requirement was 50 mu L and no internal standard was employed. Quantification was carried out with selected ion reaction (SIR) monitoring of the protonated sodium ion adduct (m/z = 1224.7). Calibration curves were linear from 0.5 ng/mL to 20 ng/mL with a weighting factor of 1/x. Precision and accuracy, and reverse predicted concentration residuals were within 15%. The method has been used successfully for the analysis of CSF samples from a clinical study.