Simultaneous determination of fixed dose combination of nebivolol and valsartan in human plasma by liquid chromatographic-tandem mass spectrometry and its application to pharmacokinetic study.
A rapid, sensitive and accurate liquid chromatographic-tandem mass spectrometry method is described for the simultaneous determination of nebivolol and valsartan in human plasma. Nebivolol and valsartan were extracted from plasma using acetonitrile and separated on a C18 column. The mobile phase consisting of a mixture of acetonitrile and 0.05 mM formic acid (50:50 v/v, pH 3.5) was delivered at a flow rate of 0.25 ml/min. Atmospheric pressure ionization (API) source was operated in both positive and negative ion mode for nebivolol and valsartan, respectively. Selected reaction monitoring mode (SRM) using the transitions of m/z 406.1-->m/z 150.9; m/z 434.2-->m/z 179.0 and m/z 409.4-->m/z 228.1 were used to quantify nebivolol, valsartan and internal standard (IS), respectively. The linearity was obtained over the concentration range of 0.01-50.0 ng/ml and 1.0-2000.0 ng/ml and the lower limits of quantitation were 0.01 ng/ml and 1.0 ng/ml for nebivolol and valsartan, respectively. This method was successfully applied to the pharmacokinetic study of fixed dose combination (FDC) of nebivolol and valsartan formulation product after an oral administration to healthy human subjects.
Selvan
P Senthamil
PS
Bioequivalence Study Centre, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700 032, India. senthamil77@yahoo.com
Gowda
K Veeran
KV
Mandal
U
U
Solomon
W D Sam
WD
Pal
T K
TK
D000284:Administration, Oral; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D001578:Benzopyrans / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D002853:Chromatography, Liquid / Q000379:methods*; D004338:Drug Combinations; D004983:Ethanolamines / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D000068577:Nebivolol; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013777:Tetrazoles / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000068756:Valsartan
D000959:Antihypertensive Agents; D001578:Benzopyrans; D004338:Drug Combinations; D004983:Ethanolamines; D013777:Tetrazoles; D000068577:Nebivolol; D000068756:Valsartan; D014633:Valine