title: High-performance liquid chromatography tandem mass spectrometry method for quantification of endothelin receptor antagonist drug, ambrisentan, in human plasma and its application in a pharmacokinetic study.
abstract: A simple and sensitive liquid chromatography tandem mass spectrometry method has been developed for the quantification of ambrisentan (AMB) in human plasma using midazolam (MID) as an internal standard (IS). Chromatographic separation was performed using a Beta Basic-8 (50 × 4.6 mm, 5 µm) column with an isocratic mobile phase. AMB and MID were detected with proton adducts at m/z 379.09 → 303.12 and 326.15 → 291.14 in multiple reaction monitoring-positive mode, respectively. A solid-phase extraction method was used for extraction of the analyte and IS from the plasma samples. The method was shown to be reproducible and reliable with within-run precision <11%, between-run precision <14% and linear concentration range from 10.0 to 2000.2 ng/mL, with a correlation coefficient (r(2) ) of >0.995. The method was successfully applied to a pharmacokinetic study of oral administration of AMB (10 mg) in 24 healthy Indian male human volunteers under fasting conditions.
authors.affiliation: LifeSan Clinical Research, Division of Centaur Pharmaceuticals Pvt. Ltd, Centaur House, Near Hotel Grand Hyatt, Vakola, Santacruz (E), Mumbai, 400055, India.
authors.forename: Ojit Kumar
authors.initials: OK
authors.lastname: Lukram
authors.forename: Ramkishor
authors.initials: R
authors.lastname: Sharma
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D018592:Cross-Over Studies; D004355:Drug Stability; D006801:Humans; D016014:Linear Models; D008297:Male; D010666:Phenylpropionates / Q000097:blood* / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics*; D011724:Pyridazines / Q000097:blood* / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D010666:Phenylpropionates; D011724:Pyridazines; C467894:ambrisentan
keywords: LC-MS/MS; ambrisentan; human plasma; pharmacokinetics; solid-phase extraction