title: Sensitive LC-MS/MS-ESI method for simultaneous determination of nifedipine and atenolol in human plasma and its application to a human pharmacokinetic study.
abstract: A rapid, simple, sensitive and selective LC-MS/MS method has been developed and validated for quantification of nifedipine (NF) and atenolol (AT) in human plasma (250 μL). The analytical procedure involves a one-step liquid-liquid extraction method using carbamazepine as an internal standard (IS). The chromatographic resolution was achieved on a Hypurity Advance C(18) column using an isocratic mobile phase consisting of 5 mm ammonium acetate-acetonitrile (15:85, v/v) at flow rate of 1.0 mL/min. The LC-MS/MS was operated under the multiple-reaction monitoring mode using electrospray ionization. The total run time of analysis was 2 min and elution of NF, AT and IS occurred at 0.79, 1.04 and 0.76 min, respectively. A detailed method validation was performed as per the FDA guidelines and the standard curves found to be linear in the range of 1.02-101 ng/mL for NF and 5.05-503 ng/mL for AT, with a coefficient of correlation of ≥ 0.99 for both the drugs. NF and AT were found to be stable in a battery of stability studies, viz. bench-top, auto-sampler and repeated freeze-thaw cycles. The validated assay method was successfully applied to a pharmacokinetic study in humans.
authors.affiliation: College of Pharmaceutical Sciences, Andhra University, Visakhapatnam-530 003, A.P., India.
authors.forename: Raja Reddy
authors.initials: RR
authors.lastname: Kallem
authors.forename: Jaswanth Kumar
authors.initials: JK
authors.lastname: Inamadugu
authors.forename: Mullangi
authors.initials: M
authors.lastname: Ramesh
authors.forename: J V L N
authors.initials: JV
authors.lastname: Seshagirirao
mesh_terms: D001262:Atenolol / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D016014:Linear Models; D059625:Liquid-Liquid Extraction; D008297:Male; D009543:Nifedipine / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D001262:Atenolol; D009543:Nifedipine