title: Plasma pharmacokinetics and lung distribution of tetrahydropalmatine after topical application of cold asthma recipe extract: Feishu (BL 13) versus Non-Feishu acupoint.
abstract: BACKGROUND
  Acupoint application of cold asthma recipe (CAR) was a traditional Chinese medicine (TCM) method, widely used as an alternative medicine for clinical prevention of the common winter diseases of asthma and bronchitis. Tetrahydropalmatine (THP) was a main active ingredient of CAR extract. The aim of this study is to compare plasma pharmacokinetics and lung distribution of THP between Feishu (FS) acupoint (BL 13) and Non-Feishu (NFS) acupoint application of CAR extract by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).
  
  
  METHODS
  The extract of CAR was topically administrated in FS and NFS acupoint of rats for plasma pharmacokinetics, and topically administrated in FS and NFS acupoint of mice for lung distribution. The plasma and lung homogenates were pretreated by protein precipitation with acetonitrile. Chromatographic separation was performed on an ACQUITY UPLC BEH C18 column with a mobile phase consisted of 0.1% formic acid in acetonitrile and 0.1% formic acid in water. The detection was accomplished by multiple-reaction monitoring (MRM) scanning in the positive electrospray ionization (ESI(+)) mode. All pharmacokinetic parameters were estimated by non-compartmental analysis.
  
  
  RESULTS
  A sensitive, accurate and precise UPLC-MS/MS method was successfully established for determination of THP in 100 μL plasma and lung homogenate. The lower limit of quantification (LLOQ) of THP was 0.05 ng/mL and 0.072 ng/mL, respectively. The pharmacokinetic results manifested that THP was absorbed and eliminated slowly in plasma. Additionally, it was found that there was significantly higher amount of THP absorbed into blood and lung after FS acupoint application compared to NFS acupoint application.
  
  
  CONCLUSIONS
  Both of the rat plasma pharmacokinetics and mice lung distribution of THP could support that FS acupoint application of CAR extract has greater advantages of absorption into the blood circulation and distribution in target tissue over NFS acupoint application. The results might be helpful in providing a rational explanation for why the TCM chose the acupoint application and elucidating the underlying mechanism of this treatment.
authors.affiliation: School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Yuan-yuan
authors.initials: YY
authors.lastname: Lin
authors.affiliation: The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yin-ping
authors.initials: YP
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Hao-yang
authors.initials: HY
authors.lastname: Lu
authors.affiliation: School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Xiu-cai
authors.initials: XC
authors.lastname: Guo
authors.affiliation: School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Chuan-bin
authors.initials: CB
authors.lastname: Wu
authors.affiliation: School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou 510006, China. Electronic address: lssxyh@mail.sysu.edu.cn.
authors.forename: Yue-hong
authors.initials: YH
authors.lastname: Xu
mesh_terms: D015669:Acupuncture Points; D000287:Administration, Topical; D000818:Animals; D001249:Asthma / Q000097:blood / Q000188:drug therapy; D001600:Berberine Alkaloids / Q000097:blood / Q000493:pharmacokinetics*; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008516:Medicine, Chinese Traditional / Q000379:methods*; D051379:Mice; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001600:Berberine Alkaloids; D004365:Drugs, Chinese Herbal; C014215:tetrahydropalmatine
keywords: Acupoint; Lung distribution; Palmatine hydrochloride (PubChem CID: 73442); Pharmacokinetics; Tetrahydropalmatine; Tetrahydropalmatine (PubChem CID: 72301); UPLC-MS/MS