Simultaneous determination of the acid/base antihypertensive drugs celiprolol, bisoprolol and irbesartan in human plasma by liquid chromatography.
A simple, rapid method for the simultaneous determination of cardiovascular drugs: celiprolol, bisoprolol and irbesartan in human plasma is described. The two main features of the proposed method deal first, with a simultaneous solid phase extraction of weakly basic beta-blockers derivatives and irbesartan which exhibit weak acidic properties; second with an absorbance monitoring using diode array detection in order to insure an improved selectivity. The separation is performed on a C(18) Kromasil 4.6 mm x 150 mm column using a linear gradient to achieve an entire separation of the four species in less than 20 min. The full analytical validation is performed according to guidance for industry for bioanalytical method validation. Linearity of the response was demonstrated for each drug for a range fulfilling the reported plasma levels, that is 10-500, 5-250 and 20-1000 ng l(-1) for celiprolol, bisoprolol and irbesartan respectively. Intra- and inter-day relative standard deviations for all compounds were, in any case, lower than 11% and the method exhibits a convenient accuracy (percentage of relative error lower than 6% for each drug). In each case, the LOD were sufficient to detect post dose trough concentrations for checking patient's observance. Moreover, selectivity towards either endogenous species or co-administered drugs was demonstrated by combination of the use of the solid phase extraction process, gradient elution and diode array detection facilities, making thus, the proposed technique especially suitable for routine drug monitoring of resistant hypertensive patients.
Caudron
E
E
Laboratoire de Pharmacologie, Hôpital Européen Georges Pompidou, 20 Rue Leblanc, 75015 Paris, France.
Laurent
S
S
Billaud
E M
EM
Prognon
P
P
D000959:Antihypertensive Agents / Q000097:blood*; D001713:Biphenyl Compounds / Q000097:blood*; D017298:Bisoprolol / Q000097:blood*; D017272:Celiprolol / Q000097:blood*; D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D000077405:Irbesartan; D011786:Quality Control; D012680:Sensitivity and Specificity; D013777:Tetrazoles / Q000097:blood*
D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D013777:Tetrazoles; D017272:Celiprolol; D000077405:Irbesartan; D017298:Bisoprolol