title: LC-MS/MS method for the quantification of almotriptan in dialysates: application to rat brain and blood microdialysis study.
abstract: A sensitive LC-MS/MS method was developed and validated for the quantification of almotriptan in rat brain and blood dialysates. Almotriptan is a 5HT1B/1D receptor agonist used for the treatment of migraine pain. Method consists of rapid gradient elution program with 10mM ammonium formate (pH 3) and acetonitrile on a Xbridge column. The MRM transitions monitored were m/z 336.2-58.1 for almotriptan and m/z 448.2-285.3 for the IS. The assay was linear in the range of 0.1-20 ng/ml, with acceptable precision and accuracy along with adequate sensitivity. The between batch accuracy was in the range of 99.0-104.3% with precision in between 0.6% and 5.8%. Microdialysis is an important sampling technique, with the capability of capturing the concentrations of various analytes in different bio fluids, at a single time point. This method was applied to quantify brain and blood dialysate samples obtained from a microdialysis study of rats treated with almotriptan (10mg/kg, p.o.). In vivo recovery experiments were performed to correct the dialysate concentrations into extracellular concentrations. Mean peak dialysate concentrations of almotriptan were found to be 152 ± 78 and 7.4 ± 1.0 ng/ml in blood and prefrontal cortex, respectively. The brain penetration of almotriptan is characterized by the AUCbrain/AUCblood found to be 0.07 ± 0.05. The results revealed the importance of measuring the unbound almotriptan concentrations in the brain over the blood for understanding its PK/PD relationship.
authors.affiliation: Biopharmaceutical Research, Suven Life Sciences Ltd, Serene Chambers, Road - 5, Avenue - 7, Banjara Hills, Hyderabad 500034, India. ramakrishna_nirogi@yahoo.co.in
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Nirogi
authors.forename: Devender Reddy
authors.initials: DR
authors.lastname: Ajjala
authors.forename: Vishwottam
authors.initials: V
authors.lastname: Kandikere
authors.forename: Raghupathi
authors.initials: R
authors.lastname: Aleti
authors.forename: Hanumanth Rao
authors.initials: HR
authors.lastname: Pantangi
authors.forename: Surya Rao
authors.initials: SR
authors.lastname: Srikakolapu
authors.forename: Vijay
authors.initials: V
authors.lastname: Benade
authors.forename: Gopinadh
authors.initials: G
authors.lastname: Bhyrapuneni
authors.forename: Himabindu
authors.initials: H
authors.lastname: Vurimindi
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001921:Brain / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods*; D008297:Male; D017551:Microdialysis / Q000379:methods; D017397:Prefrontal Cortex / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D017366:Serotonin Receptor Agonists / Q000032:analysis* / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014018:Tissue Distribution; D014363:Tryptamines / Q000032:analysis* / Q000493:pharmacokinetics
chemical_list: D017366:Serotonin Receptor Agonists; D014363:Tryptamines; C409045:almotriptan