title: Determination of plasma concentrations of losartan in patients by HPLC using solid phase extraction and UV detection.
abstract: OBJECTIVE
  To establish a HPLC assay for plasma losartan and its active metabolite EXP3174 to facilitate clinical pharmacokinetic studies.
  
  
  METHODS
  the HPLC system consisted of a 250 x 2 mm i.d. C18 reversed phase column preceded by a 4 x 4 mm guard column, a UV detector set at 254 nm, and an integrator. The mobile phase was a mixture of 0.01 M ammonium phosphate: acetonitrile: methanol (6:3:1) containing 0.02 % sodium azide and 0.04% TEA, with pH adjusted to 3.2. The system was operated isocratically at ambient temperature at a flow rate of 0.3 ml/min. Losartan and its active metabolite EXP3174 were extracted from plasma using C2 bonded silica gel standard solid phase extraction.
  
  
  RESULTS
  recoveries of losartan and EXP3174 from plasma were greater than 70%. Using 0.5 ml of plasma sample, standard curves were linear from 10 to 300 ng/ml (r2 = 0.996 and 0.997 for losartan and EXP 3174, respectively). Sensitivity of the assay was < 10 ng/ml. Intra-and inter-assay variations were < 10 and 15%. respectively. The assay has been successfully applied to measuring plasma concentrations of losartan and EXP3174 in patients receiving a daily dose of losartan (50-100 mg).
  
  
  CONCLUSIONS
  The HPLC assay has adequate sensitivity, reproducibility, and specificity for clinical pharmacokinetic studies.
authors.affiliation: Pharmacokinetics and Metabolism Laboratory, College of Pharmacy, Faculty of Health Professions, Dalhousie University, Halifax, NS, Canada. pollen.yeung@dal.ca
authors.forename: P K
authors.initials: PK
authors.lastname: Yeung
authors.forename: A
authors.initials: A
authors.lastname: Jamieson
authors.forename: G J
authors.initials: GJ
authors.lastname: Smith
authors.forename: D
authors.initials: D
authors.lastname: Fice
authors.forename: P T
authors.initials: PT
authors.lastname: Pollak
mesh_terms: D000959:Antihypertensive Agents / Q000097:blood* / Q000737:chemistry / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007093:Imidazoles / Q000097:blood* / Q000737:chemistry / Q000627:therapeutic use; D019808:Losartan / Q000097:blood* / Q000737:chemistry / Q000627:therapeutic use; D013777:Tetrazoles / Q000097:blood* / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D000959:Antihypertensive Agents; D007093:Imidazoles; D013777:Tetrazoles; C066026:losartan carboxylic acid; D019808:Losartan