An LC–MS/MS method for determination of bioactive components of liquorice and Semen Strychni in rat plasma: Application to a pharmacokinetics study

Abstract

Semen Strychni is known for its treatment of rheumatic arthritis with a low therapeutic index. Liquorice contributes a lot in herb detoxification according to the traditional Chinese medicine theory. A simple, rapid, and sensitive liquid chromatography-mass spectrometric method (LC-MS) was developed and validated for simultaneous determination of main bioactive ingredients in liquorice and Semen Strychni in rat plasma. Using moclobemide and cyproterone acetate as the internal standards, the analytes were pretreated via protein precipitation with methanol. An Ultimate AQ-C18 column (3.0 μm, 3.0 × 100 mm) was employed for chromatographic separation, combining with gradient elution. The mobile phase consisted of 0.07% formic acid and 0.12% ammonium acetate in aqueous phase (A) and acetonitrile in organic phase (B). The elution program was as follows: 0-0.5 min, 20% B; 0.5-1 min, 20-60% B; 1-7 min, 60-85% B; and 7-7.5 min, returned to 20% B, then continued to 12 min. Selected reaction monitoring was performed in both positive and negative ESI. Positive mode was adopted for detection of strychnine, brucine, and moclobemide, while negative mode was used for glycyrrhizic acid, glycyrrhetinic acid, liquiritigenin, isoliquiritigenin, liquiritin, and cyproterone acetate. The method was validated for specificity, linearity, matrix effect, recovery, precision, accuracy, and stability. The results show that this method is sensitive, accurate and robust for biological matrix analysis. Moreover, the proposed method was applied to a pharmacokinetic study in Sprague-Dawley rats for investigating the mechanism of which liquorice detoxifies Semen Strychni.

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“…Though a lot of studies regarding GA quantification have been reported however, most of the studies did not report an individual determination of GA [33,34]. Few of the studies have determined GA quantification individually but still there is lack of information in terms of GA-quantification in plasma samples [35][36][37][38][39][40][41]. Lack of reliable and reproducible method for GA-determination in plasma and brain tissues (at nanogram level), is the driving factor for current research.…”

Investigation of the detoxification effect of licorice on Semen Strychni-induced acute toxicity in rats using a HPLC-Q-TOF/MS-based metabolomics approach

“…The extraction procedure of Strychni Semen and licorice was basically in accordance with Wei et al 15 and Zhang et al, 9 respectively. Extraction protocols are described briey as follows:…”

“…Meanwhile, the AUC and t 1/2 of the main active components of licorice were also changed. 9 As can be seen, most of the studies focused on the changes in the prototype compounds of Semen Strychni and the pre-protective effects of licorice, while the investigation about the disturbance of endogenous metabolites caused by Semen Strychni and the detoxication effect of licorice is less to carry out. Moreover, brucine does not fully represent the toxicological effects of Semen Strychni and the mechanism of detoxication also needs further elucidation.…”

The System Research of the Molecular Mechanism of Quyushengxin Capsule in the Treatment of Osteonecrosis of the Femoral Head

“…For example, Sparganii rhizoma is commonly used drugs for promoting blood circulation and removing blood stasis with antithrombotic, anti-inflammatory, and antifibrous tissue hyperplasia effects, which mainly contains saponins and flavonoids [6]. Strychni semen mainly contains alkaloids, terpenes, and organic acid compounds, and its main pharmacological effects are activating meridians to stop pain and eliminating stagnation and swelling [7]. Astragali radix, cinnamomi ramulus, curcumae rhizoma, and bolbostemmatis rhizoma have also been reported to have antiinflammatory and immune regulating effects [8][9][10][11].…”