Quantitative determination of oxytocin receptor antagonist atosiban in rat plasma by liquid chromatography-tandem mass spectrometry.
A kinetic study of atosiban was conducted following repeated intravenous administration in Wistar rats. Sample analysis was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) following full validation of an in-house method. Eptifibatide, a cyclic peptide, was used as an internal standard (IS). The analyte and internal standard were extracted using solid phase extraction (SPE) method. Chromatographic separation was carried out using an ACE C18 5 microm 50 mm x 4.6 mm column with gradient elution. Mass spectrometric detection was performed using TSQ Quantum ultra AM. The lower limit of quantification was 0.01 microg/ml when 100 microl rat plasma was used. Plasma concentrations of atosiban were measured at 0 (pre-dose), 2, 15, 30, 45, 60, 120 min at the dosage levels of 0.125 mg/kg (low dose), 0.250 mg/kg (mid dose), and 0.500 mg/kg (high dose), respectively. Atosiban plasma concentration measured at Day 1 showed mean peak atosiban concentration (C(max)) 0.40, 0.57, 1.95 microg/ml for low, mid and high dose treated animals and mean peak concentration on Day 28 was 0.41, 0.88, 1.31microg/ml on Day 28 for low, mid and high dose treated animals.
Kannan
Vivekanandan
V
Research and Development, 20th KM Hosur Road, Biocon Limited, Bangalore, India. vivekanandan.kannan@yahoo.co.in
Gadamsetty
Deepak
D
Rose
Madhankumar
M
Maria
Stella
S
Mustafa
Imran
I
Khedkar
Anand
A
Dave
Nitesh
N
Arumugam
Muruganandam
M
Iyer
Harish
H
D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D000077542:Eptifibatide; D005260:Female; D006727:Hormone Antagonists / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D016014:Linear Models; D010455:Peptides / Q000032:analysis / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014668:Vasotocin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics
D006727:Hormone Antagonists; D010455:Peptides; D018045:Receptors, Oxytocin; C047046:atosiban; D000077542:Eptifibatide; D014668:Vasotocin