A UPLC-MS/MS method for simultaneous quantitation of three monoterpene glycosides and four alkaloids in rat plasma: application to a comparative pharmacokinetic study of Huo Luo Xiao Ling Dan and single herb extract

Abstract

The objective of this study was to develop a sensitive and reliable ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for simultaneous quantitation of three monoterpene glycosides (paeoniflorin, alibiflorin and oxypaeoniflorin) and four alkaloids (tetrahydropalmatine, corydaline, dehydrocorydaline and berberine), the main active ingredients of Radix Paeoniae Rubra extract (RPE) and Corydalis yanhusuo extract (CYE) in Huo Luo Xiao Ling Dan (HLXLD), and to compare the pharmacokinetics of these active ingredients in normal and arthritic rats orally administrated with HLXLD or RPE/CYE alone. The analytes and internal standard (IS) (geniposide) were separated on a XBridge C18 column (150 × 4.6 mm, 3.5 µm) using gradient elution with the mobile phase consisting of methanol and 0.01% formic acid in water at a flow rate of 0.6 ml/min. The detection of the analytes was performed on Acquity UPLC-MS/MS system with an electrospray ionization and multiple reaction monitoring mode via polarity switching between negative (for monoterpene glycosides) and positive (for alkaloids) ionization mode. The lower limits of quantification were 2.5, 1, 0.5, 0.2, 0.2, 0.02 and 0.01 ng/ml for paeoniflorin, alibiflorin, oxypaeoniflorin, tetrahydropalmatine, corydaline, dehydrocorydaline and berberine, respectively. Intra-day and inter-day precision and accuracy of analytes were well within acceptance criteria (15%). The mean extraction recoveries of analytes and IS from rat plasma were all more than 83.1%. The validated method has been successfully applied to determination of the analytes. Results showed that there were remarkable differences in pharmacokinetic properties of the analytes between herbal formula and single herb group, normal and arthritic group.

Ultra‐high performance liquid chromatography with tandem mass spectrometry method for the simultaneous quantitation of five phthalides in rat plasma: Application to a comparative pharmacokinetic study of Huo Luo Xiao Ling Dan and herb‐pair extract

“…These data indicated that some ingredients in HLXLD might reduce the bioavailability of phthalides and slow down the elimination processes of five phthalides in rats. HLXLD is a decoction of 11 herbs; each of them could produce specified pharmacological effects, and might have different influences on the absorption and metabolism of the five different components . It has already been published that the absorption of the phthalide compounds was inhibited after DG‐CX and Paeonia lactiflora Pall decocted together in another Chinese formula Danggui–Shaoyao–San .…”

Determination of armepavine in mouse blood by UPLC‐MS/MS and its application to pharmacokinetic study

“…We tried columns with different lengths and diameters such as the BEH C 18 (2.1 × 50 mm, 1.7 μm) and BEH C 18 (2.1 × 100 mm, 1.7 μm) and found that the peak time and the peak effect of the former were the best (Ai et al, 2015;Cai et al, 2016;Dong, Yu, Deng, & Pan, 2016). The BEH C 18 column, a universal one for UPLC separations, was selected in this study for the trifunctionally bonded BEH particle with superior low pH stability and ultra-low column bleed over the pH range 1-12.…”

“…The BEH C 18 column uses Waters proprietary technology for end-cap packing to ensure the peak shape of basic compounds, providing sharply symmetric peaks for highest efficiency and UPLC-MS/MS detection sensitivity. We tried columns with different lengths and diameters such as the BEH C 18 (2.1 × 50 mm, 1.7 μm) and BEH C 18 (2.1 × 100 mm, 1.7 μm) and found that the peak time and the peak effect of the former were the best (Ai et al, 2015;Cai et al, 2016;Dong, Yu, Deng, & Pan, 2016). Alkaloids on the column were prone to peak tailing.…”

“…It has become one of the most important methods of pharmacokinetics (Jahne, Sampath, Butterweck, Hamburger, & Oufir, 2016;Li, Huang, Shao, Lin, & Shen, 2017;Och et al, 2017). UPLC-MS possesses the advantages of good separation performance of UPLC and giid discrimination of MS, resulting in a better analytical technique that can fully adapt to the new development of modern pharmaceutical research (Ai et al, 2015;Bolechova, Caslavsky, Pospichalova, & Kosubova, 2015).…”

Pharmacokinetic comparison of five tanshinones in normal and arthritic rats after oral administration of Huo Luo Xiao Ling Dan or its single herb extract by UPLC‐MS/MS

“…Qiu (12 g), Gentiana macrophylla Pall (12 g), Cinnamomum cassia Presl (15 g) and Glycyrrhiza uralensis Fisch (12 g) (Lao et al, 2006). Previous studies from our laboratory had been carried out on the pharmacokinetic profiles of several components in HLXLD (Wang et al, 2014;Wu et al, 2015aWu et al, , 2015bAi et al, 2015aAi et al, , 2015b, but Salvia miltiorrhiza (SM) as the sovereign drug ('Jun') in this recipe, which has effect on promoting blood circulation, alleviating pain and targeting illness, was not studied. Tanshinones (particularly tanshinone I, tanshinone IIA, tanshinone IIB, dihydrotanshinone I and cryptotanshinone) are considered as the main bioactive compounds of S. miltiorrhiza, responsible for its anti-inflammatory, analgesic effect and inhibitory effects on 5-lipoxygenase and cyclooxygenase Kim et al, 2002;Cao et al, 2010).…”