title: Rapid and sensitive HPLC-MS/MS method for pharmacokinetic assessment of ribavirin in healthy Chinese.
abstract: A rapid and sensitive quantitative assay method was developed for determining ribavirin pharmacokinetic in human plasma. The chromatographic separation was achieved within 4.5 min using a SinoChrom ODS-BP column (4.6 x 150 mm, 5 microm) with acetonitrile-water (1 mmol/L ammonium acetate buffer, 0.1% formic acid; 15:85, v/v) at a constant flow rate of 0.8 mL/min. The MRM pairs were m/z 245.2 --> m/z 113.1 for ribavirin and m/z 226.1 --> m/z 152.1 for acyclovir (internal standard), respectively, with dwell times of 200 ms for each transition. The results showed calibration curve for ribavirin was linear over a concentration range of 1-1000 ng/mL. The lower limit of quantification (LLOQ) was 1 ng/mL ribavirin. Twenty healthy volunteers received a 300 mg oral dose of ribavirin. Blood samples were then collected up to 120 h postdosing. All plasma data were comodeled for ribavirin by using noncompartmental modeling. The single dose of ribavirin was well tolerated and no serious adverse effects occurred. The mean time to maximum concentration was about 1.25 h. The mean maximum concentration of drug in plasma for oral ribavirin was 250 ng/mL. The mean elimination half-life was 43.6 h. The present study describes a simple, specific, sensitive HPLC-MS/MS method for measuring plasma drug concentration and analyzing human pharmacokinetics of ribavirin.
authors.affiliation: Research Center of Medical Sciences, Guangdong Provincial People's Hospital, Guangzhou 510080, People's Republic of China.
authors.forename: Zhi-Ling
authors.initials: ZL
authors.lastname: Zhou
authors.forename: Xi-Yong
authors.initials: XY
authors.lastname: Yu
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.forename: Huai-Yan
authors.initials: HY
authors.lastname: Peng
authors.forename: Tie-Feng
authors.initials: TF
authors.lastname: Chen
authors.forename: Qiu-Xiong
authors.initials: QX
authors.lastname: Lin
authors.forename: Zhi-Xin
authors.initials: ZX
authors.lastname: Shan
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Liu
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Deng
authors.forename: Ping
authors.initials: P
authors.lastname: Zhu
authors.forename: Xiao-Zhong
authors.initials: XZ
authors.lastname: Huang
authors.forename: Shu-Guang
authors.initials: SG
authors.lastname: Lin
mesh_terms: D000284:Administration, Oral; D000998:Antiviral Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D044466:Asian People; D002681:China; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D015203:Reproducibility of Results; D012254:Ribavirin / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000998:Antiviral Agents; D012254:Ribavirin