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UHPLC combined with Fourier‐transform ion cyclotron resonance MS metabonomic approach was employed to screen the differential components between normal rats and yeast‐induced pyrexia rats after an oral administration of Gegenqinlian decoction (GQLD). Nine compounds, namely puerarin, daidzein, baicalin, wogonoside, wogonin, berberine, palmatine, jateorhizine, and coptisine, were identified as differential components in the plasma. A rapid, sensitive, selective, and accurate UHPLC–MS method was developed and fully validated for the simultaneous determination of the screened components in rat plasma after an oral administration of GQLD. The values for the limit of quantification ranged from 0.025 to 5.0 ng/mL. The inter‐ and intra‐day precision of all analytes was ≤10.7%, with an accuracy of ≤10.5%. Good extraction recovery and matrix effects were also obtained. The method was successfully applied to a comparative pharmacokinetic study of GQLD in normal and pyrexia rats. The results showed that the pharmacokinetic behavior of the analytes was changed in pyrexia rats compared to normal rats. These results could provide beneficial guidance for clinical applications of GQLD. [ABSTRACT FROM AUTHOR]

Abstract A sensitive and robust LC-MS/MS method has been developed and validated to simultaneous determine the concentrations of tumulosic acid, dehydrotumulosic acid, polyporenic acid C, cinnamic acid, Atractylenolide I, Atractylenolide II, Atractylenolide III, glycyrrhizic acid, glycyrrhetinic acid, liquiritigenin and isoliquiritin in plasma from rats who received Ling-Gui-Zhu-Gan Decoction extract oral administration. The samples were prepared by a liquid-liquid extraction procedure using ethyl ether as the extraction solvent and schisandrin as the internal standard. Chromatographic separation was achieved using a Thermo Hypersil GOLD C 18 column (2.1 mm × 100 mm, 1.9 µm) and a gradient mobile phase consisting of acetonitrile-water with 0.1% formic acid. All of the analytes were quantified using negative and positive multiple reaction monitoring mode. The method was validated for selectivity, linearity, accuracy, precision, recovery, matrix effect and sample stability under various storage conditions, whose values are all fell in the acceptable limits. We report the lowest limit of quantification for tumulosic acid, dehydrotumulosic acid and polyporenic acid C as 2 ng/mL. This is the first study for simultaneous determination of so many analytes in rat plasma after oral administration of Ling-Gui-Zhu-Gan Decoction. This validated method was successfully used to study the pharmacokinetics of multiple compounds in rat plasma after oral administration of Ling-Gui-Zhu-Gan Decoction. Graphical abstract fx1 Highlights • Simultaneous determination of eleven compounds in rat plasma by UPLC-MS/MS. • The pharmacokinetic study of LGZGD is reported. • The lowest limit of quantification for tumulosic acid, dehydrotumulosic acid and polyporenic acid C as 2 ng/mL. • Rapid, sensitive, selective and accurate. [ABSTRACT FROM AUTHOR]

A sensitive and selective method based on gas chromatography hyphenated to mass spectrometry (GC–MS) was developed and validated for the determination of atractylon in rat plasma. Plasma samples were processed by liquid–liquid extraction with ethyl acetate- n -hexane (1:1, v/v) using acetophenone as an internal standard (IS). Analytes were determined in selective ion monitoring (SIM) mode using target ions at m / z 108.1 for atractylon and m / z 105.1 for acetophenone. The calibration curve was linear over the concentration range of 10–1000 ng/mL with lower limit of quantification of 10 ng/mL. The intra- and inter-day precision variations were not more than 10.4% and 9.6%, respectively, whilst accuracy values ranged from −6.5% to 4.9%. Extraction recovery of the assay was satisfactory. This method was successfully applied to quantification and pharmacokinetic study of atractylon in rat plasma after intragastric administration of Atractylodis extract. [ABSTRACT FROM AUTHOR]

A simple and rapid ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed for the simultaneous determination of cinnamaldehyde, cinnamic acid, and 2-methoxy cinnamic acid in rat whole blood. It was the first time to study the pharmacokinetics of 2-methoxy cinnamic acid in rat whole blood. Samples were processed by a one-step protein precipitation with acetonitrile-37% formaldehyde (90:10, v:v). Chromatographic separation was performed on a Thermo Scientific C18 column (2.1 mm × 50 mm, 1.9 μm) at room temperature. The total run time was 4 min. The detection was accomplished by using positive and negative ion electrospray ionization in multiple reaction monitoring mode. The method was linear for all of the analytes over 1000 times concentration range with correlation coefficients greater than 0.99. The lower limits of quantification (LLOQ) were 0.1 ng/mL for cinnamaldehyde, 5.8 ng/mL for cinnamic acid, and 10 ng/mL for 2-methoxy cinnamic acid, respectively. To our knowledge, this was the first time that the LLOQ for cinnamaldehyde in validated methods for biological samples was as low as 0.1 ng/mL. Intra- and inter-day precision and accuracy were within ±9% for all of the analytes during the assay validation. Assay recoveries were higher than 80% and the matrix effects were minimal. The half-life were 8.7 ± 0.7 h for cinnamaldehyde, 1.0 ± 0.5 h for cinnamic acid, and 1.4 ± 0.4 h for 2-methoxy cinnamic acid, respectively. The validated assay was firstly applied to the simultaneous quantification of cinnamaldehyde, cinnamic acid, and 2-methoxy cinnamic acid, especially for 2-methoxy cinnamic acid in rat whole blood after oral administration of 15 mg/kg essential oil of Cinnamoni Ramulus. It was observed that the C max and AUC of 2-methoxy cinnamic acid (0.01% in essential oil of Cinnamoni Ramulus) were greater than those of cinnamaldehyde (83.49% in essential oil of Cinnamoni Ramulus), which implied that 2-methoxy cinnamic acid might be the major bioactive constitutes in essential oil of Cinnamoni Ramulus. [ABSTRACT FROM AUTHOR]

TM-2 is a novel semi-synthetic taxane derivative, selected for preclinical development based on its greater anticancer activity and lower toxicity compared with docetaxel. In this study, a rapid and sensitive analytical method based on ultra performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the determination of TM-2 in rat plasma. The biological samples were extracted with methyl tert-butyl ether and separated on a C18 column (50 mm × 2.1 mm, 1.7 µm) using a mobile phase consisting of acetonitrile and 2 mM ammonium acetate. The standard curves were linear over the range 5-1000 ng/mL in rat plasma. The precision (relative standard deviation, RSD, %) were within 14.5%, and the accuracy (relative error, RE, %) ranged from −1.56 to 2.36%. Recovery and matrix effect were satisfactory in rat plasma. The validated method was successfully applied to pharmacokinetic studies after intravenous administration of TM-2 to rats. The pharmacokinetics of TM-2 in rats were characterized by a large volume of distribution and a long half-life of elimination after single dose (4, 8, and 16 mg/kg), and a good correlation was observed between AUC and dose. The preclinical data will be useful for the design of subsequent trials of TM-2. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT A simple and sensitive method based on ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been developed for the determination of TM-2, which was a novel semi-synthetic taxane derivative in beagle dog plasma. Cabazitaxel was chosen as internal standard. Following extraction by methyl tert-butyl ether, the chromatographic separation was achieved on a Thermo Syncronis C18 column (50 × 2.1 mm, 1.7 µm) by gradient elution within a runtime of 3.5 min. The mobile phase consisted of (A) acetonitrile and (B) 2 mmol/L ammonium acetate in water. The detection was accomplished using positive ion electrospray ionization in multiple reaction monitoring mode. The MS/MS ion transitions were monitored at m/ z 812.39 → 551.35 for TM-2 and 836.36 → 555.26 for IS, respectively. The method was linear for TM-2 ( r = 0.9924) ranging from 2.5 to 1000 ng/mL. The intra-day and inter-day precisions (relative standard deviation) were within 8.0 and 17.6%, respectively, and the accuracy (relative error) was less than 2.3%. The extraction recovery ranged from 83.1 to 97.1%. The reliable method was successfully applied to a pharmacokinetic study of TM-2 in beagle dogs after intravenous drip with different doses of 0.6, 1.2, and 2.4 mg/kg, respectively. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT The study was aimed to investigate the effects of single and multiple oral administration of mungbean ( Phaseolus radiatus L.) seed extract (ME) on the pharmacokinetics of aconitine in rats. The Sprague-Dawley rats were randomly divided into three groups (six rats each group). In group 1, rats were orally administered 500 µg/kg aconitine after receiving a single oral dose of 1 g/kg ME. In group 2, rats were orally administered with 500 µg/kg aconitine at day 7 of treatment with 1 g/kg/day ME. In group 3, rats were orally administered with 500 µg/kg aconitine. Blood samples were collected at different time points (0.083, 0.25, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0 and 10.0 h). The concentration of aconitine in rats plasma was determined by a fully validated ultra-high-performance liquid chromatography coupled with mass spectrometry method. The results showed that single and multiple oral co-administration of ME significantly altered the pharmacokinetic parameters of aconitine. Copyright © 2014 John Wiley & Sons, Ltd. [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]

Highlights: [•] Simultaneous determination of puerarin glucuronide, puerarin and daidzin in rat plasma. [•] An UPLC–MS/MS method was developed and applied for pharmacokinetic study. [•] Comparative pharmacokinetics was performed in rats under different physiological states. [•] Blood stasis syndrome had effect on pharmacokinetics of puerarin glucuronide, puerarin and daidzin. [•] Pharmacokinetics of the three constituents changed when Gegen was used in combination with Sanqi. [Copyright &y& Elsevier]

Abstract: In order to investigate the preclinical pharmacokinetics of cefuroxime lysine, a fast, sensitive and high throughput UPLC–ESI–MS/MS method has been developed and validated for the quantitative determination of cefuroxime in dog plasma. Cefuroxime and IS phenacetin were extracted from plasma samples by PPT or LLE procedure, and then separated on an ACQUITY UPLC™ BEH C18 column with an isocratic elution of acetonitrile–0.1% formic acid in 10mM ammonium acetate (40:60, v/v). MRM using the fragmentation transitions of m/z 442→364 and 180→110 in positive ESI mode was performed to quantify cefuroxime and IS, respectively. The calibration curves were linear over the concentration range of 2–400μg/ml for PPT and 0.01–5μg/ml for LLE. The LLOQ was 0.01μg/ml. The intra- and inter-day precisions in all samples were no more than 8.1%, while the accuracy was within ±6.2% of nominal values. The method was successfully applied to the evaluation of pharmacokinetic parameters of cefuroxime lysine in beagle dogs. [Copyright &y& Elsevier]

Abstract: A novel amphiphilic copolymer, folate-poly(PEG-cyanoacrylate-co-cholesteryl cyanoacrylate) (FA-PEG-PCHL) was synthesized to modify docetaxel-loaded nanostructured lipid carrier to lead to a long blood circulating effect and targeting ability for the delivery of antitumor drug in cancer. To investigate the characteristics of modified docetaxel-loaded nanostructured lipid carrier in vivo, a liquid chromatography–mass spectrometry method was developed and validated for the determination of docetaxel in rat plasma and tumor-bearing mouse tissue samples. The biosamples were extracted by liquid–liquid extraction method with ether and separated on a C18 column (150mm×4.6mm, 5μm) using a mobile phase consisting of methanol–0.01% formic acid water (82:18, v/v). The standard curves were linear over the ranges of 0.01–4.0μg/mL for plasma and 0.02–8.0μg/g for tissue samples, respectively. The validated method was successfully applied to the pharmacokinetic study in rat plasma and tissue distribution study in mouse tissues of docetaxel after an intravenous administration of docetaxel injection (DTX injection), docetaxel-loaded nanostructured lipid carrier (DTX-NLC) and FA-PEG-PCHL-modified docetaxel-loaded nanostructured lipid carrier (FA-DTX-NLC), respectively. The results indicated that the FA-DTX-NLC led to significant differences in pharmacokinetic profile and tissue distribution. Nanostructured lipid carrier modified by FA-PEG-PCHL could be one of the promising suspensions for the delivery of docetaxel in cancer. [Copyright &y& Elsevier]

Abstract A selective, sensitive and fully validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established for the determination of dihydromyricetin, dihydroquercetin, myricetin and quercetin in rat plasma after intragastric administration of Hoveniae Semen total flavonoids. Baicalin was selected as the internal standard. Analytes were extracted from the rat plasma by protein precipitation with acetonitrile and separated on a C18 chromatographic column (Agilent ZORBAX Eclipse Plus, 4.6 mm × 100 mm, 3.5 μm) using the mobile phase containing acetonitrile (A) and 0.1% formic acid-water (B) by gradient elution at 0.5 mL/min flow rate. A tandem mass spectrometer equipped with an electrospray ionization (ESI) source was used to detect analytes. The analytes were measured by multiple reaction monitoring (MRM) in the negative ionization mode. The lower limit of quantification of dihydromyricetin, dihydroquercetin, myricetin and quercetin were 0.70, 8.16, 1.62 and 0.56 ng/mL, respectively. The accuracy, intra-day and inter-day precision and recovery were all satisfactory and the compounds were stable in rat plasma under all tested conditions. The approach was successfully applied to study pharmacokinetic characteristics of the four bioactive flavonoids in plasma after administering Hoveniae Semen total flavonoids intragastrically to rat. Further investigation was carried out to assess pharmacokinetic comparability of the four bioactive flavonoids after intragastric administration of Hoveniae Semen total flavonoids to mixture of flavonoids. Highlights • Pharmacokinetics of 4 main flavonoids in Hoveniae Semen were determined. • Only 6.5 min was in need for one analytical run. • The pharmacokinetic of Hoveniae Semen was firstly studied. • Comparative pharmacokinetics of Hoveniae Semen total flavonoids and a mixture of flavonoids were firstly investigated. [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]

A high-performance liquid chromatography tandem mass spectrometry (HPLC–MS/MS) method was developed and fully validated for simultaneous determination of puerarin, 3′-hydroxy puerarin, 6″- O -xylosyl puerarin, 3′-methoxy puerarin, mirificin, puerarin-7- O -glucoside, daidzin, daidzein, daidzein-7- O -glucoside, ginsenoside-Rd, notoginsenoside-R1, ginsenoside-Re, ginsenoside-Rg1, ginsenoside-Rb1 in rat plasma after intravenous injection of 5 mL/kg Gegen-Sanqi compatibility solution (containing Pueraria flavonid 10.8 mg/mL and Panax notoginsenosidum 5.4 mg/mL). After addition of internal standard (IS) baicalin, the analytes and IS were recovered from rat plasma by protein precipitation using acetonitrile containing 0.1% formic acid. Chromatographic separation was performed on a Capcell pak MG C18 column (3.0 mm × 75 mm, 3.0 μm) at 35 °C with a flow rate of 0.75 mL/min. Mass spectrometry was conducted using multiple reaction monitoring in positive mode. The method was linear for all of the analytes over 1000 times concentration range with correlation coefficients greater than 0.99. The precision and accuracy of the LC–MS/MS assay based on the three analytical quality control (QC) levels were well within the acceptance criteria from FDA guidance for bioanalytical method validation. Method recoveries were higher than 75% and the matrix effects were minimal. All analytes were stable under tested conditions. It was the first time to study the pharmacokinetics of daidzein-7- O -glucoside in rat plasma. To the best of our knowledge, this is the first study for simultaneous determination of so many analytes in rat plasma after intravenous injection of Gegen-Sanqi compatibility solution. It was expected that the present work would provide some helpful references for the apprehension of the mechanism of action and further clinical efficacy studies of Gegen-Sanqi herb-pair. [ABSTRACT FROM AUTHOR]

"Four Natures and five "Flavors" comes from the high generalization of medicine pharmacological rules from clinical practice by ancients. "Flavor" and "Natures"are both descriptions of the effect properties of traditional Chinese medicine. At present, researchers have realized that the "Flavors" (Pungent, Sour, Sweet, Bitter and Salty) are related to the different pharmacological effects of treatment. The "Natures" (Warm, Hot, Cold and Cool) are closely related to energy and substance metabolism and contribute to the effect of the "Flavors". Since "Four Natures and five Flavors" are the rules derived from clinical practice, how to describe and characterize "Natures" and "Flavors" scientifically is still a problem that needs to be solved. the aim is to objectively further understand the scientific connotations of properties ("Flavors"and "Natures") from the perspective of metabolomics and characterize them by metabolites. "Pungent-Neutral", "Sweet-Neutral and "Bitter-Neutral" TCMs were selected to characterize the "Flavors" (Pungent, Sweet and Bitter). "Pungent-Warm" and "Bitter-Cold" were selected to characterize the "Natures" (Warm and Cold). The rat serum metabolomics was performed on UHPLC-Q-Exactive. Metabolites were identified through the metabolites databases and related literature. The "Flavors" and "Natures" metabolites were identified, respectively, including four "Pungent", four "Sweet" and thirteen "Bitter" characterized metabolites and thirteen "Cold" and sixteen "Warm"related metabolites. The "Natures" characterized metabolites show the "Natures" are closely related to lipid and energy metabolism. The "Warm" may promote lipid metabolism to produce ATP to generate energy through bile acid metabolism and purine metabolism. The "Cold" may inhibit lipid metabolism to generate ATP to decrease energy through the way of tryptophan metabolism and purine metabolism. The "Flavors" characteristic metabolites can provide a theoretical basis for the rules of the "Flavors". These metabolites can also be used to characterize TCM's "Natures" and "Flavors" in the development of traditional Chinese medicine resources and quality control. [Display omitted] • The metabolomics-integrated strategies were used to characterize the Chinese medicine "Flavors" and "Natures". • "Pungent,Sweet and Bitter" and "Warm and Cold" medicines were selected to study the "Flavors" and"Natures" respectively. • The "Flavors" characteristic metabolites were screened out by PCA and OPLS-DA, The "Natures" are related to lipid metabolism. [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 simple and sensitive UHPLC–MS/MS method was developed and validated to determine the pharmacokinetic profile of 2-(2-hydroxypropanamido) benzoic acid (HPABA) enantiomers and their prodrugs in rat plasma. Separation was performed on a Thermo Syncronis C 18 column (50 mm × 2.1 mm, 1.7 μm; Thermo, USA), which was protected by a high pressure column prefilter (2 μm) at a flow rate of 0.4 ml/min. Liquid-liquid extraction with ethyl acetate was used to process plasma samples. The separation of two enantiomers, prodrugs of ( R ) -/ ( S )-HPABA and internal standard was obtained within a cycle time of 4.5 min. The lower limit of quantification of ( R ) -/ ( S )-HPABA and prodrugs of ( R ) -/ ( S )-HPABA in plasma were 0.01 μg/ml and 0.2 μg/ml, respectively. ( S )-HPABA showed significantly higher AUC, C max and a longer t 1/2 than ( R )-HPABA, indicating higher bioavailability of the ( S )-HPABA. Additionally, inversion between HPABA enantiomers was not observed in rats. ( R ) -/ ( S )-HPABA showed higher C max and AUC than those of their prodrugs. However, the values of t 1/2 of prodrugs were higher than those of ( R ) -/ ( S )-HPABA. Furthermore, the higher V z values of prodrugs might improve the targeting of ( R ) -/ ( S )-HPABA in rat tissues. [ABSTRACT FROM AUTHOR]

In Hedera helix hederacoside C, hederacoside D, and ɑ-hederin are three major bioactive saponins and play pivotal roles in the overall biological activity. In this study, a specific and sensitive ultra-high performance liquid chromatography with tandem mass spectrometry method has been developed and validated for the quantification of three major bioactive saponins in rat plasma. Chromatographic separation was performed on a reversed-phase Thermo Hypersil GOLD C18 column (2.1 mm × 50 mm, 1.9 μm) using a gradient mobile phase system of acetonitrile-water containing 0.1% formic acid. The assay was successfully applied to study the pharmacokinetic behavior of the three analytes in rats after oral and intravenous administration of a mixture of saponins (hederacoside C, hederacoside D, and ɑ-hederin). Further research was performed to compare the pharmacokinetic behavior of the three analytes after the oral administration of a mixture of saponins and an extract of saponins from Hedera helix, and results showed that double peaks were evident on concentration-time profile for each of the three saponins. The difference in the pharmacokinetic characteristics of three saponins between a mixture of saponins and an extract of saponins from Hedera helix was found in rat, which would be beneficial for the preclinical research and clinical use of Hedera helix. [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]

A simple and rapid ultra high performance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS) method was developed for the simultaneous determination of Atractylenolide I, II and III in rat plasma. Plasma samples were processed by liquid–liquid extraction with ethyl acetate, using schisandrin as internal standard (IS). Chromatographic separation was accomplished on a Thermo Hypersil GOLD C 18 column (2.1 mm × 50 mm, 1.9 μm) with mobile phase consisting of acetonitrile and 0.1% formic acid–water (50:50, v/v ). The detection was carried out by ESI-MS (positive ionization mode) and low-energy collision dissociation tandem mass spectrometric analyses using the multiple-reaction monitoring (MRM) scan mode. The quantification was performed using the transitions of the protonated molecule → product ion at m / z 231.0 → 185.1 for Atractylenolide I, at m / z 233.1 → 187.1 for Atractylenolide II and at m / z 249.1 → 231.1 for Atractylenolide III, respectively. Method validation revealed excellent linearity over investigated range together with satisfactory intra- and inter-day precision, accuracy, matrix effects and extraction recoveries. This method was successfully applied to the comparative pharmacokinetic study of Atractylenolide I, II and III in rat plasma after intragastric administration of Baizhufuling extract and Atractylodis extract. [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]

Highlights: [•] Development and validation of an UHPLC–ESI-MS/MS method for the determination of dictamnine in rat plasma and tissues. [•] The method was successfully applied to study pharmacokinetics, tissue distribution and excretion of dictamnine in rats. [•] Optimal assay conditions gave detection levels in the range of 0.5–250ng/mL. [ABSTRACT FROM AUTHOR]

Highlights: [•] The report describes the validation of a high precision and accuracy UPLC–MS/MS method for the simultaneous determination of limonin, dictamnine, obacunone and fraxinellone in rat plasma. [•] The pharmacokinetic study of Cortex Dictamni in rats is firstly reported. [•] Extraction performed with a simple liquid–liquid extraction. [•] Sensitivity, specificity and high throughput. [Copyright &y& Elsevier]