title: A quantitative LC-MS/MS method for determination of SP-141, a novel pyrido[b]indole anticancer agent, and its application to a mouse PK study.
abstract: In the present study, a specific and sensitive liquid chromatography-triple quadrupole mass spectrometry method was developed and validated for the determination of SP-141, a novel pyrido[b]indole anticancer agent. After a liquid-liquid extraction with n-hexane-dichloromethane-2-propanol (20:10:1, v/v/v) mixture, the analyte was separated on a Kinetex C18 column (50×2.1mm, 2.6μm) with mobile phases comprising of water (0.1% formic acid, v/v) and acetonitrile (0.1% formic acid, v/v) at a flow rate of 0.4mL/min. The test compound (SP-141) and the internal standard (SP-157) were analyzed in the multiple reaction-monitoring mode using the mass transitions m/z 325.1 → 282.0. The method was linear in the concentration range of 0.648-162ng/mL with coefficients of determination (R(2)) of 0.999 in mouse plasma. The lower limit of quantification was 0.648ng/mL. The intra- and inter-day assay precisions (coefficient of variation, %CV) were less than 4.2% and accuracies (relative error, %RE) ranged from -6.1% to 2.1%. The extraction recoveries were between 97.1 and 103.1% and the relative matrix effect was minimal. In addition, SP-141 was found to be stable in the plasma after three freeze-thaw cycles, at 37°C and 4°C for 24h, and at -80°C for 4 weeks. It was also stable in the stock solution at room temperature for 24h and after preparation in the autosampler for 36h. The validated method was successfully applied to an initial pharmacokinetic study of SP-141 in CD-1 mice following intraperitoneal and intravenous administrations.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA.
authors.forename: Subhasree
authors.initials: S
authors.lastname: Nag
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA.
authors.forename: Jiang-Jiang
authors.initials: JJ
authors.lastname: Qin
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Shivaputra
authors.initials: S
authors.lastname: Patil
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Hemantkumar
authors.initials: H
authors.lastname: Deokar
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: John K
authors.initials: JK
authors.lastname: Buolamwini
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA.|Cancer Biology Center, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA.|Cancer Biology Center, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA.
authors.forename: Ruiwen
authors.initials: R
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D007211:Indoles / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D016014:Linear Models; D051379:Mice; D011725:Pyridines / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C000593082:6-methoxy-1-(naphthalen-1-yl)-9H-pyrido(3,4-b)indole; D000970:Antineoplastic Agents; D007211:Indoles; D011725:Pyridines
keywords: LC-MS/MS; Mouse plasma; Pharmacokinetics; Pyrido[b]indole; SP-141