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Dictamnine, a furoquinoline alkaloid isolated from the root bark of Dictamnus dasycarpus Turcz. (Rutaceae), is reported to have a wide range of pharmacological activities. In this study, the in vitro metabolic profiles of dictamnine in mouse, rat, dog, monkey, and human liver microsomes were investigated and compared. Dictamnine was incubated with liver microsomes in the presence of an NADPH-regenerating system, resulting in the formation of eight metabolites (M1–M8). M1 is an O -desmethyl metabolite. M5 and M6 are formed by a mono-hydroxylation of the benzene ring of dictamnine. M8 was tentatively identified as an N -oxide metabolite. The predominant metabolic pathway of dictamnine occurs through the epoxidation of the 2,3-olefinic to yield a 2,3-epoxide metabolite (M7), followed by the ring of the epoxide opening to give M4. Likewise, cleavage of the furan ring forms M2 and M3. Slight differences were observed in the in vitro metabolic profiles of dictamnine among the five species tested. A chemical inhibition study with a broad and five specific CYP450 inhibitors revealed that most of the dictamnine metabolites in liver microsomes are mediated by CYP450, with CYP3A4 as the predominant enzyme involved in the formation of M7, the major metabolite. These findings provide vital information to better understand the metabolic processes of dictamnine among various species. [ABSTRACT FROM AUTHOR]

Highlights: [•] Development of a UHPLC–MS/MS method to determine HPABA in rat plasma. [•] The total analysis time was 2.0min. [•] The method was applied to pharmacokinetic study of HPABA in rats. [•] HPABA showed linear pharmacokinetic properties and high absolute bioavailability. [ABSTRACT FROM AUTHOR]

Abstract: A liquid chromatographic–mass spectrometric (LC–MS) method was developed and validated for the simultaneous determination of homoeriodictyol-7-O-β-d-glycoside (HEDT-Glc) and its active metabolite homoeriodictyol (HEDT) in rat tissues and urine. The analytes and internal standard (dihydromyricetin, IS) were detected by using negative atmospheric pressure chemical ionization mass spectrometry in selected ion monitoring (SIM) mode at m/z 464, 301 and 319 for HEDT-Glc, HEDT and IS, respectively. These compounds were eluted on a Luna reverse phase column. The mobile phase was a methanol–water mixture (70:30, v/v) containing 0.1% of formic acid at a flow rate of 0.8ml/min. The limit of quantification (LOQ) for both HEDT-Glc and HEDT was 10ng/ml and their limit of detection (LOD) was 1ng/ml. Calibration curves were linear (r >0.995) over a wide range of the analytes in tissues and urine. The mean extraction recoveries were ≥75.6% for HEDT-Glc and ≥82.4% for HEDT from biological matrixes. Accuracy, expressed as the relative error, ranged from −4.0% to 3.8% for HEDT-Glc and from −2.8% to 4.7% for HEDT. The method was successfully applied to the estimation of HEDT-Glc and its metabolite HEDT in rat tissues and urine. [Copyright &y& Elsevier]

• An UHPLC-FT-ICR-MS method was developed for metabonomic analysis of incompatible GS-GC. • A total of 20 metabolites were recognized as the toxic biomarkers of GS-GC. • GSBXD can attenuate the toxicity of GS-GC by 7 metabolic pathways. • The mechanisms of GS-GC and GSBXD were firstly elucidated in plasma metabonomics. Gansui-Gancao is one of the "eighteen incompatible herb pairs" which was recorded 2000 years ago according to TCM (Traditional Chinese Medicine) theory for their toxicity when using together. Nevertheless, Gansuibanxia decoction contained the herb pair have satisfactory effect on the treatment of cancerous ascites, pericardial effusion, etc. The present study aimed to investigate the mechanism of the incompatibility of Gansui-Gancao and the compatibility of Gansuibanxia decoction using UHPLC-FT-ICR-MS in a metabonomic perspective. Rats were divided into four groups administrated with different herb combination extracts for successive 14 days. Orthogonal partial least squares-discriminant analysis (OPLS-DA) was used to plot the metabolic state and screen the potential biomarkers in plasma. A total of 20 biomarkers contributed to the separation of Gansui-Gancao group and control group were tentatively identified mainly involved in 7 metabolic pathways related to hepatotoxicity and nephrotoxicity. The contents of these biomarkers were adjusted to normal levels in Gansuibanxia decoction group. Thus, the results of our study reveled the mechanism of the incompatibility of Gansui-Gancao and the compatibility of Gansuibanxia decoction in a metabonomic perspective and it's valuable for better understanding the "eighteen incompatible madicaments" of TCM theory. [ABSTRACT FROM AUTHOR]

Incompatible herb pair Gansui-Gancao is recorded in “eighteen incompatible” medicaments in many monographs of TCM (Traditional Chinese Medicine) which means the two herbs can not be co-used in most cases. However, Gansuibanxia decoction composed of Gansui(Kansui), Banxia(Pinellia), Shaoyao(Peony) and Gancao ( Liquorice) is a traditional Chinese formula which has been clinically employed for the treatment of cancerous ascites, pleural effusion, peritoneal effusion, etc. The purpose of the study was to investigate the pharmacokinetics of main bioactive components in Gancao to explore the reasons why Gansui-Gancao can be used in Gansuibanxia decoction. A simple, rapid and sensitive UHPLC-MS/MS method for simultaneous determination of liquiritigenin, isoliquiritigenin, liquiritin, glycyrrhetinic acid and glycyrrhizic acid of liquorice in rat plasma was developed and validated. After extraction from plasma, the analytes and internal standard were separated on a C18 column with the mobile phase consisting of 0.1% acetic acid containing 0.2 mM ammonium acetate in water and acetonitrile via gradient elution. The electrospary ionization source was adopted under the multiple reaction monitoring mode. The method was succesfully applied to a comparative pharmacokinetic study of main bioactive components of Gancao in rat plasma after oral administration of the extracts of Gancao (GC), Gansui-Gancao (GS-GC), Shaoyao-Gancao (SY-GC), Gansui-Shaoyao-Gancao (GS-SY-GC) and Gansuibanxia decoction (GSBXD), respectively. The pharmacokinetic parameters had significant differences (P < 0.05) in different groups which showed that Gansui decreased the bioavailability of Gancao, while S haoyao increased the bioavailability of Gancao. Hence, these may be the pharmacokinetic mechanism of incompatible herb pair Gansui-Gancao and the reasons why the herb pair can be used in Gansuibanxia decoction. [ABSTRACT FROM AUTHOR]

Rapid, sensitive, selective and accurate UPLC–MS/MS method was developed and fully validated for simultaneous determination of cinnamaldehyde, cinnamic acid, 2-methoxy cinnamic acid, glycyrrhizic acid, glycyrrhetinic acid, liquiritigenin and isoliquiritin in rat plasma after oral administration of Guizhi-gancao decoction. Plasma samples were processed with a simple protein precipitation technique using acetonitrile, followed by chromatographic separation using a Thermo Hypersil GOLD C 18 column. A 11.0 min linear gradient elution was used at a flow rate of 0.2 mL/min with a mobile phase of 0.1% acetic acid containing 0.2 mM ammonium acetate in water and acetonitrile. The analytes and internal standard, schisandrin, were detected using both positive and negative ion electrospray ionization in multiple reaction monitoring mode. The developed method was validated for intra-day and inter-day accuracy and precision whose values fell in the acceptable limits. Matrix effect was found to be minimal. Recovery efficiency of all the analytes was found to be >60%. Stability results showed that the analytes were stable at all the conditions. This validated method was successfully used to study the pharmacokinetics of multiple compounds in rat plasma after oral administration of Guizhi-gancao decoction. [ABSTRACT FROM AUTHOR]

A RP-HPLC method was developed and validated for the degradation kinetic study of 2-(2-hydroxypropanamido) benzoic acid (HPABA), a promising anti-inflammatory drug, which would provide a basis for further studies on HPABA. The effects of pH, temperature, buffer concentration and ionic strength on the degradation kinetics of HPABA were discussed. Experimental parameters such as degradation rate constants ( k ), activation energy ( E a ), acid and alkali catalytic constants ( k ac , k al ), shelf life ( t 1/2 ) and temperature coefficient ( Q 10 ) were calculated. The results indicated that degradation kinetics of HPABA followed zero-order reaction kinetics; degradation rate constants ( k ) of HPABA at different pH values demonstrated that HPABA was more stable in neutral and near-neutral conditions; the function of temperature on k obeyed the Arrhenius equation ( r = 0.9933) and HPABA was more stable at lower temperature; with the increase of ionic strength and buffer concentration, the stability of HPABA was decreased. The major unknown degradation product of HPABA was identified by UHPLC/TOF–MS/MS with positive electrospray ionization. Results demonstrated that the hydrolysis product was the primary degradation product of HPABA and it was deduced as anthranilic acid. [ABSTRACT FROM AUTHOR]

In order to investigate the pharmacokinetics of triamcinolone acetonide palmitate (TAP) which is a lipid-soluble prodrug of triamcinolone acetonide (TA), a rapid, simple, sensitive and reproducible UPLC-MS/MS method has been developed and validated for the simultaneous determination of TAP and TA in beagle dog plasma. After simple liquid–liquid extraction, the analytes and internal standard (dexamethasone, DEX) were separated on Phenomenex Luna C 18 column (50 mm × 2.1 mm, 1.7 μm) using a mobile phase consisting of solvent A (acetonitrile) and solvent B (0.1% ammonia solution) at a flow rate of 0.2 ml/min with gradient elution. Acquisition of mass spectrometric data was performed in multiple reaction monitoring (MRM) mode via positive electrospray ionization using the ion transitions of m/z 673.5 → 397.3, 435.3 → 415.3 and 393.3 → 355.3 for TAP, TA and IS, respectively. The method was of satisfactory specificity, sensitivity, precision and accuracy over the concentration range of 1–1000 ng/ml for TAP and 0.5–500 ng/ml for TA. The intra- and inter-day precisions for both TAP and TA were 3.2% to 18.7% and the accuracy was in the range of −8.4% to 6.8%. The mean recoveries of TAP, TA and IS were 86.7–104.7%. The method was successfully applied to a long-term pharmacokinetic study of TAP and TA after 28-day repeated intravenous administration of TAP lipid emulsion injection to beagle dogs. [ABSTRACT FROM AUTHOR]

• An UHPLC-FT-ICR-MS method was developed for chemical constituents characterization of GSBXD. • A total of 62 chemical constituents were detected in GSBXD. • Chemical constituents in GSBXD were first chemically defined or tentatively identified. Gansuibanxia decoction (GSBXD) is one of the most famous traditional Chinese medicine (TCM). It is a herbal formula used for treating hydrops, such as cancerous ascites, pleural effusion, pericardial effusion, etc. However, the chemical constituents of GSBXD were still unclear. In this study, an UHPLC-FT-ICR-MS method was established and applied to the separation and characterization of the chemical constituents of GSBXD. A total of 62 components were chemically defined or tentatively identified, including diterpenoids, triterpenoids, flavonoids, monoterpene glycosides and alkaloids. The results is meaningful for a better understanding of the material basis of GSBXD and can be the basis for its further in vitro and in vivo studies. [ABSTRACT FROM AUTHOR]