title: Application of a liquid chromatography-tandem mass spectrometry method to the pharmacokinetics, tissue distribution and excretion studies of sweroside in rats.
abstract: A sensitive, reliable and accurate high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) was developed and validated for the quantification of sweroside in rat plasma, tissue and excretion. A single-step protein precipitation by methanol was used to prepare samples. Sweroside and swertiamarin (internal standard, IS) were separated by using a C18 column and a mobile phase consisted of methanol and water containing 0.1% formic acid running at a flow rate of 0.8ml/min for 6min. Detection and quantification were performed using a mass spectrometer by the multiple-reaction monitoring (MRM) in positive electrospray ionization mode. The optimized mass transition ion pairs (m/z) for quantitation were [M+H](+)359.1→197.2 for sweroside and [M+Na](+)397.4→165.3 for swertiamarin (IS), respectively. The inter-day precision (RSD %) was less than 11.20% and intra-day precision (RSD %) was less than 10.90%, while the inter-day accuracy (RE %) was ranged from -9.69 to 9.17% and intra-day accuracy (RE %) was ranged from -10.56 to 13.47%. The mean elimination half-life (t1/2) of sweroside for 5, 10 and 15mg/kg dose were 78.8, 67.6 and 77.2min, respectively. And sweroside follows linear plasma pharmacokinetics across the investigated dosage range in rats (5-15mg/kg). The absolute bioavailability (F %) of sweroside was 11.90% on average. The results of tissue distribution showed the higher sweroside concentrations were found in kidney, liver, spleen and lung, and the small amount of drug was distributed into the brain tissue. The high distribution in liver confirms the reports that sweroside has hepatoprotective activity and promoted liver regeneration, and there was no long-term accumulation of sweroside in rat tissues. Total recoveries of sweroside within 48h were 0.67% in bile, 1.55% in urine and 0.46% in feces, which might be resulted from liver first-pass effect. The above results suggested that sweroside was mainly excreted as the metabolites.
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang, Hebei 050017, PR China; Department of Pharmacy, The Third Hospital of hebei Medical University, 139 Ziqiang Road, Shijiazhuang, Hebei 050051, PR China; Department of Traditional Chinese Medicine Pharmacology, School of Traditional Chinese Medicine, Hebei Medical University, 326 Xinshinan Road, Shijiazhuang, Hebei 050091, PR China.
authors.forename: Ning
authors.initials: N
authors.lastname: Sheng
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang, Hebei 050017, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Department of Pharmacy, Hebei General Hospital, 348 West Heping Road, Shijiazhuang, Hebei 050051, PR China.
authors.forename: Xuran
authors.initials: X
authors.lastname: Zhi
authors.affiliation: Department of Pharmacy, Hebei General Hospital, 348 West Heping Road, Shijiazhuang, Hebei 050051, PR China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Cui
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang, Hebei 050017, PR China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang, Hebei 050017, PR China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Jia
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang, Hebei 050017, PR China.
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang, Hebei 050017, PR China. Electronic address: zhanglantong@263.net.
authors.forename: Lantong
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Traditional Chinese Medicine Pharmacology, School of Traditional Chinese Medicine, Hebei Medical University, 326 Xinshinan Road, Shijiazhuang, Hebei 050091, PR China. Electronic address: wangxinguozy@163.com.
authors.forename: Xinguo
authors.initials: X
authors.lastname: Wang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D057888:Iridoid Glucosides / Q000008:administration & dosage / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics*; D057230:Limit of Detection; D016014:Linear Models; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014018:Tissue Distribution
chemical_list: D057888:Iridoid Glucosides; C049412:sweroside
keywords: Excretion study; LC–ESI-MS/MS; Pharmacokinetics; Sweroside; Tissue distribution