Liquiritin Apioside

Pharmacokinetics study of 16 representative components from Baoyuan Decoction in rat plasma by LC-MS/MS with a large-volume direct injection method.[Pubmed:30668317]

Phytomedicine. 2018 Sep 13;57:148-157.

BACKGROUND: Baoyuan decoction (BYD), a well-known traditional Chinese medicine (TCM) formula, is clinically used for the treatment of aplastic anemia, chronic renal failure, coronary heart disease, etc. PURPOSE: The purpose of this study was to develop a large-volume direct injection liquid chromatography-mass spectrometry (LC-MS) method for simultaneous determination of 16 representative flavonoids and saponins in rat plasma after oral administration of BYD. METHODS: The rat plasma sample was injected directly into a pre-column, which was eluted firstly by 0.05% formic acid in water. Then, the accumulated components were eluted from the pre-column and transferred into a Waters BEH C18 column with acetonitrile and water system (contain 0.05% formic acid) as the mobile phase at a rate of 0.3ml/min. The detection was accomplished in a negative mode using the schedule multiple-reaction monitoring (sMRM). RESULTS: The correlation coefficients for calibration curves were all higher than 0.9920 for formononetin, ononin, calycosin, liquiritigenin, isoliquiritigenin, glycyrrhizic acid, glycyrrhetinic acid, liquiritin, isoliquiritin, Liquiritin Apioside, isoLiquiritin Apioside, ginsenoside Rb1, ginsenoside Re, ginsenoside Rd, ginsenoside Rg1 and astragaloside. The intra- and inter-day precisions (RSD) and accuracy (RE) for the investigated components were in the range of -10.9 to 13.7%. The average recoveries were in the range of 75.7-108.6%. This method was successfully applied to investigate the pharmacokinetics of 16 compounds of BYD in rats. The absorption and elimination rates of the representative saponins were significantly slower than most of the targeted-flavonoids after oral administration of BYD in rats. CONCLUSION: The results demonstrated that the large-volume direct injection LC-MS method provided a rapid and efficient approach for multi-components pharmacokinetics of TCM.

Isoliquiritin Apioside Suppresses in vitro Invasiveness and Angiogenesis of Cancer Cells and Endothelial Cells.[Pubmed:30618749]

Front Pharmacol. 2018 Dec 10;9:1455.

Several components isolated from Glycyrrhizae radix rhizome (GR), including glycyrrhizin, liquiritin, and liquiritigenin, have been shown to induce cancer cell death and inhibit cancer metastasis. IsoLiquiritin Apioside (ISLA), a component isolated from GR, has been effective for treating tetanic contraction and genotoxicity. However, the effects of ISLA on the metastasis and angiogenesis of malignant cancer cells and endothelial cells (ECs) have not been reported. In this study, we found that up to 100 muM ISLA did not affect cell proliferation but efficiently suppressed the metastatic ability of HT1080 cells, as assessed by scratch-wound migration, Transwell((R)) migration, scratch-wound invasion, Transwell((R)) invasion, and three-dimensional spheroid invasion. ISLA significantly decreased phorbol 12-myristate 13-acetate (PMA)-induced increases in matrix metalloproteinase (MMP) activities and suppressed PMA-induced activation of mitogen-activated protein kinase as well as NF-kappaB, which are involved in cancer metastasis. In addition, ILSA treatment reduced the production of pro-angiogenic factors in HT1080 cells, including MMP-9, placental growth factor, and vascular endothelial growth factor under normoxia as well as hypoxia conditions, by impairing the hypoxia-inducible factor-1alpha pathway. We also found that the abilities of human umbilical vein ECs to migrate across the Transwell((R)) and to form tube-like structures were significantly reduced by ISLA treatment. Moreover, using the chorioallantoic membrane assay, vessel formation with or without vascular endothelial growth factor was significantly suppressed by ISLA. These results suggested that ISLA possesses anti-metastatic and anti-angiogenic abilities in malignant cancer cells and ECs, with no cytotoxicity. ISLA may therefore be a safe and effective lead compound to develop anti-cancer drug for limiting the spread of primary tumors to distant organs to form secondary tumors.

Chemical profiling by LC-MS/MS and HPLC fingerprint combined with chemometrics and simultaneous determination of 16 characteristic ingredients for the quality consistency evaluation of Shaoyao-Gancao Decoction.[Pubmed:30277266]

Biomed Chromatogr. 2019 Feb;33(2):e4401.

In this paper, to evaluate the effect of the region of origin on the quality consistency of Shaoyao-Gancao Decoction (SGD), the SGD fingerprint was developed for the first time. Chemometric methods including similarity analysis, hierarchical clustering analysis and principal component analysis were employed to study the quality consistency of SGD. Meanwhile, high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry was applied for comprehensive analysis of SGD and 93 compounds were tentatively characterized. Furthermore, a high-performance liquid chromatography method with multi-wavelength switching for simultaneous determination of 16 characteristic ingredients comprising gallic acid, oxypaeniflorin, albiflorin, paeoniflorin, Liquiritin Apioside, liquiritin, isoLiquiritin Apioside, galloylpaeoniflorin, 1,2,3,4,6-penta-O-galloyl-d-galactopyranose (PGG), ononin, isoliquiritin, liquiritigenin, benzoylpaeoniflorin, glycyrrhizic acid, isoliquiritigenin and formononetin, was established. All 16 analytes show excellent linearity (R(2) >/= 0.9990) with recoveries ranging from 96.58 to 104.61% and limits of detection and quantification of 0.022-0.291 and 0.037-0.635 mug/mL, respectively. Finally, it was successfully applied to determine 15 batches of SGD. The results of our research indicate that different regions of origin have a significant effect on the quality consistency of SGD, and its fingerprint combined with chemometrics and multi-ingredient determination comprise an efficient and reliable approach for quality consistency evaluation.

Effect of seedling grade standard on improving the quality of licorice (Glycyrrhiza uralensis F.): changes in the seven bioactive components and root biomass during two-year growth.[Pubmed:30263822]

Food Sci Biotechnol. 2018 Mar 3;27(4):939-945.

Licorice cultivated is one of the most popular herbal medicines, while its quality is unstable. The aim of present study is to investigate the effect of licorice seedling grade standard on improving its quality. One-year-old Glycyrrhiza uralensis seedlings were classified into three grades 1, 2, and 3 by weight per plant. The major root biomass indexes (root fresh weight, root dry weight and taproot diameter) and contents of 7 bioactive components (glycyrrhizin, liquiritin, Liquiritin Apioside, liquiritigenin, isoliquiritin, isoLiquiritin Apioside, and isoliquiritigenin) varied in different grades seedlings. Further, the contents of 7 investigated compounds of 3-year-old licorice produced by grade 1 seedlings were 1.5-2 times as much as those produced by grade 2 and 3. Additionally, the contents of Liquiritin Apioside and isoLiquiritin Apioside were positively correlated with licorice root biomass. These results indicated that establishing licorice seedling grade standard is an effective way to improve and control its quality.

Rapid screening and identification of bioactive compounds specifically binding to beta 2-adrenoceptor from San-ao decoction using affinity magnetic fine particles coupled with high-performance liquid chromatography-mass spectrometry.[Pubmed:30258489]

Chin Med. 2018 Sep 24;13:49.

Background: San-ao decoction (SAD) has been widely used in Chinese medicine against respiratory diseases, such as asthma and rhinallergosis. The bioactive compounds for such pharmacological action remain unknown. Methods: We developed a methodology to isolate the bioactive compounds of SAD. The assay involved the immobilization of beta 2-adrenoceptor (beta 2-AR) onto magnetic fine particles, the capture of target compounds by the immobilized receptor, the identification of the receptor bound compounds by reversed-phase high-performance liquid chromatography coupled with tandem mass spectrometry. Results: Vicenin, shaftoside, isoshaftoside, Liquiritin Apioside and isoLiquiritin Apioside were identified as beta 2-AR ligands in SAD extract. The binding of these compounds to beta 2-AR occurred on serine(169), serine(170) and phenylalanine(256) of the receptor. Conclusions: The developed methodology has high stability and specificity for recognizing and isolating target compounds. It is an alternative method for rapidly screening bioactive compounds of immobilized receptor from Chinese prescriptions.

The Effects of the Honey-Roasting Process on the Pharmacokinetics of the Six Active Compounds of Licorice.[Pubmed:30034498]

Evid Based Complement Alternat Med. 2018 Jun 21;2018:5731276.

A convenient UPLC-MS/MS method was established to determine the contents of six bioactive compounds, namely, Liquiritin Apioside, liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin, and glycyrrhetinic acid, in rat plasma and their pharmacokinetics. By comparing the pharmacokinetic parameters of these compounds in rats by orally administering raw and honey-roasting licorice, the Cmax of isoliquiritin showed a significant decrease, while the AUC0-24h showed no significant differences. The Cmax and AUC0-24h of isoliquiritigenin were increased by 49.3% and 42.7% over those of the raw licorice group, respectively. These results indicate that the absorption of isoliquiritin in rats was reduced while the absorption of isoliquiritigenin was promoted in the honey-roasting process. These results may provide one explanation as to why licorice is more able to relieve cough, while honey-roasting licorice is better at invigorating qi and restoring pulse. Furthermore, the Cmax of glycyrrhetinic acid was increased, suggesting that it may enhance the tonic effect of licorice. Additionally, the amount of honey added in the honey-roasting process influenced the pharmacokinetic parameters of the six compounds whose absorption decreased when the 50% honey-roasting licorice water decoction was administered. These results provide an experimental basis for studying the influence of licorice processing on bioactive compound pharmacokinetics.

Simultaneous Determination of the Traditional Herbal Formula Ukgansan and the In Vitro Antioxidant Activity of Ferulic Acid as an Active Compound.[Pubmed:29986512]

Molecules. 2018 Jul 7;23(7). pii: molecules23071659.

Ukgansan (UGS), a traditional herbal formula composing seven medicinal herbal plants, has been applied in Asian countries for treating neurosis, insomnia, and irritability. Here, the current study performed a simultaneous determination of the seven marker compounds (Liquiritin Apioside, liquiritin, ferulic acid, glycyrrhizin, decursin, decursinol angelate, and atractylenolide I) using high-performance liquid chromatography (HPLC), to establish quality control of UGS. A 70% ethanol extract of UGS and a mixture of the seven compounds were separated using a C-18 analytical column on a gradient solvent system of 1.0% (v/v) aqueous acetic acid and acetonitrile. Data were recorded at a UV wavelength of 250 nm for glycyrrhizin; 276 nm for Liquiritin Apioside, liquiritin, and atractylenolide I; and 325 nm for ferulic acid, decursin, and decursinol angelate. The results exhibited high linearity (correlation coefficient (r(2)) ≥ 0.9998) and proper precision (0.38(-)3.36%), accuracy (95.12(-)105.12%), and recovery (95.99(-)104.94%) for the seven marker compounds. The amount of the seven marker compounds at the concentrations from 0.190 to 16.431 mg/g. In addition, the current study evaluated the antioxidant effects of UGS by measuring their scavenging activities against the 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2′-diphenyl-1-picrylhydrazyl (DPPH) radicals using in vitro cell-free systems and observed its antioxidant activity. Among the seven components of the UGS extract, ferulic acid dramatically enhanced the scavenging of ABTS and DPPH radicals compared with other compounds. The concentrations of ferulic acid required for a 50% reduction (RC50) in ABTS and DPPH radicals were 16.22 μM and 41.21 μM, respectively. Furthermore, UGS extract exerted the neuroprotective effect and blocked the inflammatory response in neuronal hippocampal cells and microglia, respectively. Overall, the established method of HPLC will be valuable for improving the quality control of UGS extract, and ferulic acid may be useful as a potential antioxidant agent.

Chemical Profile and Anti-inflammatory Activity of Total Flavonoids from Glycyrrhiza Uralensis Fisch.[Pubmed:29881429]

Iran J Pharm Res. 2018 Spring;17(2):726-734.

Glycyrrhiza uralensis Fisch. (G. uralensis) is one of the most widely used herbal medicines. This study was designed to enrich total flavonoids (TFF) from G. uralensis. The chemical profile of TFF was identified by HPLC and colorimetric assay. The TFF mainly contained Liquiritin Apioside, liquiritin, isoLiquiritin Apioside, liquiritigenin and isoliquiritigenin without glycyrrhizic acid. To study the anti-inflammatory activity of TFF, the DMB-induced ear vasodilatation assay and carrageenan-induced rat paw edema model have been utilized. Treatment with TFF showed significant anti-inflammatory activities in the two models. The two in-vivo edema assays demonstrated that the TFF possesses significant dose-dependent anti-inflammatory activity, similar to that of indomethacin at a dose of 500 mg/kg. In rat paws with carrageenan, treatment with TFF (500 and 250 mg/kg) markedly inhibited the expression of IL-1beta and iNOS. TFF at all doses noticeably decreased levels of NO and MDA at the site of inflammation, while only i.g. TFF at a dose of 500 mg/kg significantly decreased TNF-alpha levels in the carrageenan-injected paws. In addition, an increase in SOD activity was induced by TFF at all doses. These results revealed that TFF exhibited significant anti-inflammatory activity in acute inflammatory models.

Pretreatment with broad-spectrum antibiotics alters the pharmacokinetics of major constituents of Shaoyao-Gancao decoction in rats after oral administration.[Pubmed:29773886]

Acta Pharmacol Sin. 2019 Feb;40(2):288-296.

The influence of broad-spectrum antibiotics on the pharmacokinetics and biotransformation of major constituents of Shaoyao-Gancao decoction (SGD) in rats was investigated. The pharmacokinetic behaviors of paeoniflorin (PF), albiflorin (AF), liquiritin (LT), isoliquiritin (ILT), Liquiritin Apioside (LA), isoLiquiritin Apioside (ILA), and glycyrrhizic acid (GL), seven major constituents of SGD, as well as glycyrrhetinic acid (GA), a major metabolite of GL, were analyzed. A 1-week pretreatment with broad-spectrum antibiotics (ampicillin, metronidazole, neomycin, 1 g L(-1); and vancomycin, 0.5 g L(-1)) via drinking water reduced plasma exposure of the major constituents. The AUC0-24 h of PF and LT was significantly decreased by 28.7% and 33.8% (P < 0.05 and P < 0.005), respectively. Although the differences were not statistically significant, the AUC0-24 h of AF, ILT, LA, ILA, and GL was decreased by 31.4%, 50.9%, 16.9%, 44.1%, and 37.0%, respectively, compared with the control group. In addition, the plasma GA exposure in the antibiotic-pretreated group was significantly lower (P < 0.005) than the control group. The in vitro stability of the major constituents of SGD in the rat intestinal contents with or without broad-spectrum antibiotics was also investigated. The major constituents were comparatively stable in the rat duodenum contents, and the biotransformation of GL mainly occurred in the rat colon contents. In summary, broad-spectrum antibiotics suppressed the absorption of the major constituents of SGD and significantly inhibited the biotransformation of GL to GA by suppressing the colon microbiota. The results indicated a potential clinical drug-drug interaction (DDI) when SGD was administered with broad-spectrum antibiotics.

Paljung-San, a traditional herbal medicine, attenuates benign prostatic hyperplasia in vitro and in vivo.[Pubmed:29501675]

J Ethnopharmacol. 2018 May 23;218:109-115.

ETHNOPHARMACOLOGICAL RELEVANCE: Paljung-san is a traditional herbal medicine used widely for the treatment of urogenital diseases in East Asia. However, scientific evidence of the efficacy of Paljung-san and its mechanisms of action against benign prostatic hyperplasia (BPH) is not clearly established. AIM OF THE STUDY: We investigated the inhibitory effect of Paljung-san water extract (PSWE) and its mechanisms against BPH in vitro and in vivo. MATERIALS AND METHODS: Active compounds of PSWE were analyzed quantitatively by High-performance liquid chromatography (HPLC). For in vitro study, PSWE treated BPH-1 cells were used to perform western blot analysis, cell cycle analysis and enzyme-linked immunosorbent assay. For in vivo BPH model, male rats were subcutaneously injected with 10mg/kg of testosterone propionate (TP) every day for four weeks. 200 and 500mg/kg of PSWE was administrated daily by oral gavage with s.c. injection of TP, respectively. RESULTS: HPLC revealed that PSWE contains 1.21, 1.18, 2.27, 3.56, 4.23, 3.00, 6.78, and 0.004mg/g of gallic acid, 5-caffeoylquinic acid, chlorogenic acid, geniposide, Liquiritin Apioside, liquiritin, glycyrrhizin, and chrysophanol components, respectively. In human BPH-1 cells, PSWE treatment reduced cell proliferation through arresting the cell cycle in the DNA synthesis phase. Moreover, PSWE suppressed prostaglandin E2 production with reduced cyclooxygenase-2 expression. In TP -induced BPH rat model, PSWE administration showed reduced prostate weights and dihydrotestosterone levels and led to a restoration of normal prostate morphology. PSWE also decreased TP-induced Ki-67 and cyclin D1 protein levels in the prostatic tissues. Decreased glutathione reductase activity and increased malondialdehyde levels in the BPH groups were reversed by PSWE administration. CONCLUSION: PSWE attenuates the progression of BPH through anti-proliferative, anti-inflammatory and anti-oxidant activities in vitro and in vivo. Therefore, these data provide the scientific evidence of pharmacological efficacy of PSWE against BPH.

The effect of ethanol extract of Glycyrrhiza uralensis on the voltage-gated sodium channel subtype 1.4.[Pubmed:29433959]

J Pharmacol Sci. 2018 Feb;136(2):57-65.

To investigate the inhibitory effect of Glycyrrhiza uralensis (G. uralensis) and its monomeric compounds on Nav1.4 voltage-gated sodium channels (VGSCs) and analyze the relationship between the content of its marker compounds and the inhibitory rate. Based on this study, we found that 4 mg/ml ethanol extract of G. uralensis at 30%, 50%, 70% and 90% (v/v) exhibited 77.00 +/- 0.03%, 34.75 +/- 0.09%, 100.00 +/- 0.01% and 2.00 +/- 0.01% inhibitory rates on INav1.4 respectively, and 8 mg/ml ethanol extract of G. uralensis at 30%, 50%, 70% and 90% (v/v) exhibited 99.00 +/- 0.01%, 97.10 +/- 0.02%, 100.00 +/- 0.01% and 17.00 +/- 0.04% inhibitory rates on INav1.4 respectively. Isoliquiritigenin, echinatin, liquiritin and glycyrrhizic acid exhibited higher inhibitory rates of 39.98 +/- 4.55%, 33.20 +/- 1.61%, 22.62 +/- 0.30% and 20.54 +/- 4.82% respectively. However, liquiritigenin, formononetin, neoisoliquiritin and glycyrrhetinic acid exhibited lower inhibitory rates of less than 20%. Further, Liquiritin Apioside, isoliquiritin and neoliquiritin exhibited almost no effect on INav1.4. These findings showed that glycyrrhizic acid reached a maximum concentration of 49.15 mug/ml, while echinatin had the lowest concentration. The ethanol extract of G. uralensis has significant inhibitory effects on Nav1.4 VGSCs. This may be an important mechanism in the treatment of gastrocnemius spasm and could guide further research regarding material basis and mechanism of the treatment of gastrocnemius spasm with peony and licorice decoction.

Antitussive and expectorant activities of licorice and its major compounds.[Pubmed:29224994]

Bioorg Med Chem. 2018 Jan 1;26(1):278-284.

Licorice has been used as an antitussive and expectorant herbal medicine for a long history. This work evaluated the activities of 14 major compounds and crude extracts of licorice, using the classical ammonia-induced cough model and phenol red secretion model in mice. Liquiritin Apioside (1), liquiritin (2), and liquiritigenin (3) at 50mg/kg (i.g.) could significantly decrease cough frequency by 30-78% (p<.01). The antitussive effects could be partially antagonized by the pretreatment of methysergide or glibenclamide, but not naloxone. Moreover, compounds 1-3 showed potent expectorant activities after 3days treatment (p<.05). The water and ethanol extracts of licorice, which contain abundant 1 and 2, could decrease cough frequency at 200mg/kg by 25-59% (p<.05), and enhance the phenol red secretion (p<.05), while the ethyl acetate extract showed little effect. These results indicate Liquiritin Apioside and liquiritin are the major antitussive and expectorant compounds of licorice. Their antitussive effects depend on both peripheral and central mechanisms.

Simultaneous Quantification of Eight Marker Compounds in Yongdamsagan-Tang Using a High-Performance Liquid Chromatography Equipped with Photodiode Array Detector.[Pubmed:29048491]

J Chromatogr Sci. 2017 Oct 1;55(9):926-933.

Yongdamsagan-tang (YDSGT) has been used clinically for the treatment of acute- and chronic-urethritis, cystitis, orchitis and hypertension in Korea. In this study, a powerful method based on high-performance liquid chromatography (HPLC) with photodiode array (PDA) detection was established and validated for the quantitative analysis of eight components: chlorogenic acid, gentiopicroside, Liquiritin Apioside, liquiritin, nodakenin, baicalin, wogonoside and glycyrrhizin in YDSGT extract. The compounds were separated with a Gemini C18 analytical column (column temperature: 40 degrees C; mobile phase: 0.1% (v/v) aqueous trifluoroacetic acid (A) and acetonitrile (B); flow rate: 1.0 mL/min; injection volume: 10 muL). The PDA detector scanned the range 190-800 nm and the marker compounds were monitored at 254, 275, 325 and 335 nm. The correlation coefficients of all compounds were 1.000 and the results showed excellent linearity. The lower limits of detection and quantification of the analytes were 0.01-0.09 mug/mL and 0.03-0.28 mug/mL, respectively. The extraction recoveries of the marker compounds were 98.13-103.86%, with relative standard deviation values not exceeding 2.10%. The precision of intra- and inter-day measurements were 0.09-1.78% and 0.12-2.09%, respectively. The content of the eight marker compounds in the freeze-dried YDSGT extract were 1.41-23.71 mg/g.

Intestinal Absorption of Triterpenoids and Flavonoids from Glycyrrhizae radix et rhizoma in the Human Caco-2 Monolayer Cell Model.[Pubmed:28961192]

Molecules. 2017 Sep 29;22(10). pii: molecules22101627.

Glycyrrhizae radix et rhizoma has been used as a traditional Chinese medicine for the treatment of various diseases. Triterpenoids and flavonoids from the plant have many beneficial effects and their chemical structures are modified in the gastrointestinal tract after oral administration. However, absorption of these triterpenoids and flavonoids still needs to be defined. Here, the uptake and transepithelial transport of the selected major triterpenoids, glycyrrhizin (1), glycyrrhetic acid-3-O-mono-beta-d-glucuronide (2), and glycyrrhetinic acid (3); and the selected major flavonoids, licochalcone A (4), licochalcone B (5), licochalcone C (6), echinatin (7), isoLiquiritin Apioside (8), liquiritigenin (9), Liquiritin Apioside (10) isolated from Glycyrrhizae radix et rhizoma, were investigated in the human intestinal epithelium-like Caco-2 cell monolayer model. Compounds 3, 5-7, and 9 were designated as well-absorbed compounds, 2 and 4 were designated as moderately absorbed ones, and 1, 8, and 10 were assigned for the poorly absorbed ones. The absorption mechanism of well and moderately absorbed compound was mainly passive diffusion to pass through the human intestinal Caco-2 cell monolayer. These findings provided useful information for predicting their oral bioavailability and the clinical application.

Simultaneous Determination of 11 Compounds in Gualou Guizhi Granule and Pharmacokinetics Study by UPLC-MS/MS.[Pubmed:28808600]

J Anal Methods Chem. 2017;2017:8451383.

A rapid and sensitive ultrafast performance liquid chromatography-tandem mass spectrometry method (UPLC-MS/MS) was developed for the simultaneous determination of 11 compounds in Gualou Guizhi Granule (GLGZG), including liquiritin, isoliquiritin, liquirtin apioside, isoLiquiritin Apioside, liquiritigenin, isoliquiritigenin, glycyrrhizic acid, glycyrrhetinic acid, paeoniflorin, albiflorin, and paeoniflorin sulfonate in rat plasma. UPLC-MS/MS assay with negative ion mode was performed on a Waters CORTECS C18 (2.1 x 100 mm, 1.6 mum) with the mobile phase consisting of 0.1% aqueous formic acid (A) and acetonitrile (B) in gradient elution at a flow rate of 0.25 mL.min(-1). The method was linear for all analytes within the detection range (r >/= 0.9597). The inter- and intraday precision (RSD) were 2.21-6.41% and 1.67-6.18%; the inter- and intraday accuracy (recover) were 92.48-114.03% and 90.23-112.04%. And the recovery rate ranged from 81.30% to 108.22%. The matrix effect values obtained for analytes ranged from 88.91% to 113.32%. This validated method was successfully applied to a pharmacokinetics study in rats after oral administration of GLGZG.