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Quantification of OSU-2S, a novel derivative of FTY720, in mouse plasma by liquid chromatography-tandem mass
Yicheng Mao1, Jiang Wang2, Yuan Zhao2
1College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA; Nanoscale Science and Engineering Center for Affordable Nanoengineering of Polymeric Biomedical Devices (CANPBD), The Ohio State University, Columbus, OH 43210, USA.
Abstract:
OSU-2S is a novel anti-cancer and immune modulatory agent designed specifically to avert the immunosuppressive effects and related toxicities observed in clinical studies with its predecessor analog, FTY720. To characterize its preclinical pharmacokinetics, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of OSU-2S in mouse plasma. Ethyl acetate extraction of samples containing OSU-2S and the internal standard, Sph-17, was followed by separation with a 6min gradient (water/0.1% formic acid and methanol/0.1% formic acid) on a reverse-phase C18 column at room temperature. Selected reaction monitoring was used for detection on a triple quadrupole mass spectrometer with positive ionization. The assay was linear over the concentration range 3-3000ng/mL with accuracy ranging from 103 to 111%, and both within- and between-run precision (CV%) ≤11%. All stability samples were within ±15% of nominal values, and replicates were within 15% CV. The assay was successfully applied to a mouse pharmacokinetic study of OSU-2S with intravenous and intraperitoneal administration. OSU-2S non-compartmental pharmacokinetic parameters, area under the concentration-time curve, clearance, and elimination half-life were estimated at 1522hμg/L, 3.06L/h/kg and 15.6h, respectively, for intravenous injection. Systemic availability after intraperitoneal injection was approximately 46%. These data demonstrate the OSU-2S compound displays acceptable pharmacokinetic properties for further in vivo pharmacologic evaluation, which can be facilitated by the validated LC-MS/MS assay.
Insights
A new cancer drug, OSU-2S, shows promising pharmacokinetics in mice. A validated LC-MS/MS method confirms its suitability for further preclinical studies.
Area of Science:
- Pharmacology and Toxicology
- Analytical Chemistry
- Immunology
Background:
- OSU-2S is a novel anti-cancer and immune modulatory agent.
- It aims to overcome toxicities associated with FTY720.
- Preclinical pharmacokinetic characterization is essential for drug development.
Purpose of the Study:
- To develop and validate a quantitative LC-MS/MS method for OSU-2S in mouse plasma.
- To assess the pharmacokinetic profile of OSU-2S in mice following different administration routes.
Main Methods:
- Liquid chromatography-tandem mass spectrometry (LC-MS/MS) with positive ionization.
- Ethyl acetate extraction and C18 reverse-phase column separation.
- Validation included linearity, accuracy, precision, and stability assessments.
Main Results:
- The LC-MS/MS assay was linear (3-3000 ng/mL) with high accuracy (103-111%) and precision (CV% ≤11%).
- Pharmacokinetic parameters for intravenous injection: AUC 1522 h·μg/L, CL 3.06 L/h/kg, t1/2 15.6 h.
- Intraperitoneal administration showed approximately 46% systemic availability.
Conclusions:
- The validated LC-MS/MS assay is suitable for quantifying OSU-2S in mouse plasma.
- OSU-2S exhibits acceptable pharmacokinetic properties for further in vivo evaluation.
- These findings support the continued development of OSU-2S as a potential therapeutic agent.
