DETERMINATION OF MOXONIDINE (BDF-5895) IN PLASMA BY GAS-CHROMATOGRAPHY NEGATIVE-ION CHEMICAL IONIZATION MASS-SPECTROMETRY

For the measurement of the pharmacokinetic behaviour of moxonidine, 4-chloro-5-(2-imidazolin-2-yl-amino)-6-methoxy-2-methylpyrimidine, an extremely sensitive analytical method was needed. The GC-MS method developed is specific and reliably detects moxonidine plasma levels down to 40 pg ml-1. Using negative ion chemical ionization (NICI) the M- fragment of the ditrifluoromethyl benzamide derivative of moxonidine (m/z 721) and the [M-HCl]- fragment of the ditrifluoromethyl benzamide derivative of clonidine (internal standard, m/z 673) were monitored in the selected ion monitoring mode, ensuring a specific and sensitive detection of the compounds. The validation process carried out included assay precision, repeatability, linearity, accuracy, stability and estimation of the detection and determination limits. The plasma-level time-curves and pharmacokinetic parameters from two volunteers after oral administration of 0.2 mg moxonidine are presented and demonstrate the practicability of the method in, for example, clinical studies.