Salvia miltiorrhiza, one of the most well-known herbal medicines, is commonly used for the treatment of coronary heart diseases in China. Besides traditional decoction slices (TDS), another relatively new product of S. miltiorrhiza, ultrafine granular powder (UGP; D90 < 45 μm), is also increasingly being used. In this paper, a UHPLC-LTQ-Orbitrap MS technique was developed for a metabolite profile study after oral administration of UGP and TDS of S. miltiorrhiza. The results showed that the number of in vivo absorbed compounds from UGP was much greater than that from TDS, and different types of products from S. miltiorrhiza will have different metabolic processes in vivo. Furthermore, a UHPLC-Q-Trap MS/MS method for simultaneously determining four tanshinones (tanshinone IIA, dihydrotanshinone I, tanshinone I and cryptotanshinone) was established and applied to assess the pharmacokinetics of the two types of products. All of the analytes displayed significant higher area under the concentration-time curve and peak concentration after oral administration of UGP than after TDS, indicating that ultrafine powder product could improve the bioavailability and absorption of cryptotanshinon,tanshinone II A,dihydrotanshinonE I and tanshinone I in vivo. The present study provides scientific information for further exploration of the pharmacology of these two types of S. miltiorrhiza and offers a reference for clinical administration of S. miltiorrhiza.

is one of the most used herbal medicines for the treatment of a wide range of diseases in China. Decoction pieces and Chinese patent medicines from are the two main types of products used by patients. Other relatively new products of, like injections and ultrafine granular powder (D < 45 µm before granulation), are also increasingly used nowadays. With the growing usage of new products of , their chemical components and pharmacological effects, compared to the traditional decoction pieces, are attracting attention. In this work, the chemical profiles of two types of products from (one is traditional "decoction pieces", the other is modern "ultrafine granular powder") were compared via similarity analysis and discriminated via multivariate analysis, e.g., hierarchical cluster analysis, principal component analysis, and partial least squares discrimination analysis. A new adamantane stationary phase column was used to establish informative chemical profiles of them. The mean similarity correlation coefficient (> 0.987) revealed that ultrafine granular powder and decoction pieces of were consistent between each other and stable between different batches. Two types of products were clearly resolved from each other by hierarchical cluster analysis, principal component analysis, and partial least squares discrimination analysis. Compounds responsible for the discrimination results were further characterized by ESI-MS/MS. Eventually, 62 compounds selected as characteristic markers for evaluation were characterized or tentatively characterized. This result will facilitate the further comparison of these two types of products in pharmacology and pharmacokinetics.

No abstract

No abstract

Summary.A rapid and sensitive ultraperformance liquid chromatography-multiple reaction monitoring-multi-stage/mass spectrometry (UPLC-MRM-MS/MS) method has been developed for simultaneous quantification of salvianolic acid B and tanshinone IIA of salvia tropolone tablets in dog plasma. This was achieved by performing quantification using the MRM acquisition with two channels of MRM-MS/MS and MS full scan for more accuracy qualitative results, and the fragmentation transitions of m/z 295→249, 191 for tanshinone IIA and m/z 297→279, 251 for IS in positive mode, m/z 717→519, 321 for salvianolic acid B and m/z 295→267, 239 for IS in negative mode were selected. The UPLC separation was achieved within 3 min in a single UPLC run. Linear calibration curves were obtained over the concentration range of 10 pg/mL −1 ng/mL for tanshinone IIA and 100 pg/mL −1 for salvianolic acid B. Lower limit of quantitation (LLOQ) was 10 pg/mL and 100 pg/mL for tanshinone IIA and salvianolic acid B, respectively. The inter-day and intra-day precision (relative standard deviation, RSD) in all samples were less than 8.21%, and the recoveries were over 85.9% for both tanshinone IIA and salvianolic acid B. The two channels of MRM with MS full scan approach could provide both qualitative and quantitative results without the need for repetitive analyses and resulted in the reduction of further confirmation experiments and analytical time. The pharmacokinetic study of the two active components of salvia tropolone tablets following oral gavage administration of dogs was thus explored with this method.