Plasma pharmacokinetics and lung distribution of tetrahydropalmatine after topical application of cold asthma recipe extract: Feishu (BL 13) versus Non-Feishu acupoint

Abstract

Ethnopharmacological relevanceAcupoint 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). Materials and methodsThe 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. ResultsA sensitive, accurate and precise UPLC-MS/MS method was successfully established for determination of THP in 100μL plasma and lung homogenate. The lower limit of quantification (LLOQ) of THP was 0.05ng/mL and 0.072ng/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. ConclusionsBoth 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.