Simultaneous determination of a novel oral Janus kinase inhibitor ASP015K and its sulfated metabolite in rat plasma using LC-MS/MS.
A sensitive and selective liquid chromatography with tandem mass spectrometry (LC-MS/MS) was developed for determining the concentrations of novel Janus kinase inhibitor ASP015K and its sulfated metabolite M2 in rat plasma. This method involves solid-phase extraction (SPE) from 25 μL of rat plasma. LC separation was performed on an Inertsil PH-3 column (100 mm L ×4.6 mm I.D., 5 µm) with a mobile phase consisting of 10 mM ammonium acetate and methanol under linear gradient conditions. Analytes were introduced to the LC-MS/MS through an electrospray ionization source and detected in positive-ion mode using selected reaction monitoring. Standard curves were linear from 0.25 to 500 ng/mL (r ≥0.9964). This assay enabled quantification of ASP015K and M2 at a concentration as low as 0.25 ng/mL in rat plasma. Validation data demonstrated that the method is selective, sensitive and accurate. Further, we also successfully applied this method to a preclinical pharmacokinetic study in rats.
Analysis and Pharmacokinetics Research Laboratories, Astellas Pharma Inc., 1-6 Kashima, 2-chome, Yodogawa-ku, Osaka, 532-8514, Japan.
Kazuo
K
Oda
Analysis and Pharmacokinetics Research Laboratories, Astellas Pharma Inc., 1-6 Kashima, 2-chome, Yodogawa-ku, Osaka, 532-8514, Japan.
Katsumi
K
Mera
Analysis and Pharmacokinetics Research Laboratories, Astellas Pharma Inc., 1-6 Kashima, 2-chome, Yodogawa-ku, Osaka, 532-8514, Japan.
Yasuhisa
Y
Nagasaka
Safety Research Laboratories, Astellas Pharma Inc., 1-6 Kashima, 2-chome, Yodogawa-ku, Osaka, 532-8514, Japan.
Kazumi
K
Tokoro
D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D000284:Administration, Oral; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D005260:Female; D053612:Janus Kinases / Q000037:antagonists & inhibitors*; D016014:Linear Models; D008297:Male; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013431:Sulfates / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry / Q000379:methods*
D047428:Protein Kinase Inhibitors; D013431:Sulfates; D009536:Niacinamide; D053612:Janus Kinases; C000608065:peficitinib; D000218:Adamantane
ASP015K; LC-MS/MS; pharmacokinetics; rat plasma; sulfate