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.
Rudolph
M
M
Pharmaceutical Development, Beiersdorf AG, Hamburg, Germany.
Janssen
W
W
Strassner
M
M
D000959:Antihypertensive Agents / Q000097:blood*; D004355:Drug Stability; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007093:Imidazoles / Q000097:blood*
D000959:Antihypertensive Agents; D007093:Imidazoles; C043482:moxonidine