title: Validated LC-MS/MS method for the simultaneous determination of chlorambucil and its prodrug in mouse plasma and brain, and application to pharmacokinetics.
abstract: A simple, sensitive and rapid LC-MS/MS method was developed and validated for the simultaneous determination of chlorambucil (CHL) and the prodrug of chlorambucil (CHLS) in mouse plasma and brain tissue. Detection was performed on a Diamonsil ODS chromatography column using gradient elution with a mobile phase of 0.2% aqueous formic acid and acetonitrile. Mass spectrometry was carried out in multiple reaction monitoring mode using a positive electrospray ionization interface. Good linearity was found for CHLS and CHL in plasma and brain tissue in different linear ranges (r>0.9996). Intra-day and inter-day precision was within 9.11% and accuracy was not more than 11.07%. The validated method was successfully applied to the pharmacokinetic study of CHLS and CHL in mice after intravenous administration.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, PR China.
authors.forename: XinYi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, PR China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, PR China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, PR China. Electronic address: zrzzl@vip.sina.com.
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Zhang
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D002699:Chlorambucil / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D002853:Chromatography, Liquid / Q000379:methods; D004305:Dose-Response Relationship, Drug; D057230:Limit of Detection; D008297:Male; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D018906:Antineoplastic Agents, Alkylating; D011355:Prodrugs; D002699:Chlorambucil
keywords: Brain; Chlorambucil; LC–MS/MS; Pharmacokinetics; Prodrug