title: Development and validation of a high throughput and robust LC-MS/MS with electrospray ionization method for simultaneous quantitation of diltiazem and its two metabolites in human plasma: Application to a bioequivalence study.
abstract: A high throughput and specific method using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed for the simultaneous determination of diltiazem and its two metabolite (N-desmethyldiltiazem and O-desacetyldiltiazem) in human plasma. A one-step liquid-liquid extraction (LLE) with methyl-t-butyl ether (MTBE) involved for the extraction of diltiazem (DLTZ), metabolites (DMeD and DAcD) and internal standard. Analytes were chromatographed on a ACQUITY UPLC BEH C(18) column (100 mm x 2.1 mm, i.d., 1.7 microm) with isocratic elution at a flow rate of 0.2 mL/min using 10 mM ammonium acetate buffer-acetonitrile (25:75, v/v). The Quattro Premier XE LC-MS/MS was operated under the multiple reaction-monitoring mode (MRM) using the electrospray ionization technique. Using 300 microL plasma, the method was validated over the concentration range 0.48-639.9 ng/mL for DLTZ and 0.24-320.1 for DMeD and 0.24-320.7 ng/mL for DAcD, with a lower limit of quantification of 0.48 ng/mL for DLTZ and 0.24 ng/mL for metabolites. The intra- and inter-day precision and accuracy were within 10.0%. The recovery was 77.4%, 76.0%, 74.5% and 74.1% for DLTZ, DMeD, DAcD and Ziprasidone, respectively. Total run time was 2.0 min only.
authors.affiliation: Department of Chemistry, Pilvai Science College, Pilvai, Vijapur, Gujarat State, India.
authors.forename: Bhavesh
authors.initials: B
authors.lastname: Dasandi
authors.forename: Sanjay
authors.initials: S
authors.lastname: Shah
authors.lastname: Shivprakash
mesh_terms: D001331:Automation / Q000379:methods*; D002853:Chromatography, Liquid / Q000379:methods*; D004110:Diltiazem / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013810:Therapeutic Equivalency
chemical_list: D004110:Diltiazem