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Aconiti Radix [Chuanwu (CW)] is widely used to treat chronic and intractable diseases due to its remarkable curative effect. CW has been combined with honey for thousands of years to reduce toxicity and enhance efficacy. This study first determined the compatibility mechanism of CW with honey using a comparative pharmacokinetic concept. We developed and validated a simple, sensitive, specific, and accurate UHPLC–MS/MS method to simultaneously determine five Aconitum alkaloids in rat plasma after the oral administration of CW decoction and CW–honey concentrated solution. Pharmacokinetic parameters were significantly different between the two groups (P < 0.01 and P < 0.05). Compared with the CW group, Cmax and AUC0 → t decreased in the CW–honey group for three diester‐diterpenoid alkaloids (hypaconitine, mesaconitine, and aconitine); Tmax and T1/2 were prolonged. However, Cmax and AUC0 → t increased in the CW–honey group for two monoester‐diterpenoid alkaloids (benzoylaconine and benzoylmesaconine); Tmax was shortened, and T1/2 was prolonged. These findings suggest that honey affected the pharmacokinetic behaviors of five Aconitum alkaloids. We speculate that the detoxification and synergism of honey might result from reducing the toxicity of diester‐diterpenoid alkaloids and promoting the biological activity of monoester‐diterpenoid alkaloids in vivo. This study provides a theoretical basis for the clinical use of CW combined with honey. [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]

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]

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]

Abstracts 2-(2-Hydroxypropanamido) benzoic acid (HPABA) is a potential anti-inflammatory agent isolated from the marine fungus Penicillium chrysogenum . In vivo tissue distribution and excretion of HPABA were unknown. Therefore, the purpose of this paper was to establish an UHPLC–MS/MS method for the determination of HPABA and proceed to apply for the study of tissue distribution and excretion in rats. The results obtained indicated that HPABA in tissues was rapidly distributed and cleared. The highest level was found in intestine and stomach, followed by kidney, liver, lung and heart. These observations showed that HPABA was well distributed into abundant blood-supply tissues, suggesting that the blood flow or perfusion rate of organs plays a major role. A small amount of HPABA was detected in brain indicated that the ability of it in crossing the blood brain barrier (BBB) was very weak in rats. Excretion studies demonstrated that HPABA was mainly excreted by kidney. The total cumulative excretion of HPABA were 54.3% and 44.1% in male and female rats, respectively. In addition, gender-related differences in the excretion and distribution profile of HPABA were observed in rats. [ABSTRACT FROM AUTHOR]

As the stereoselective plasma protein binding is an important factor for the differences in pharmacokinetic or pharmacodynamic properties of chiral drugs, we elucidated the binding of ( R ) -/ ( S ) - HPABA to plasma protein. A UHPLC–MS/MS method was developed and validated to the quantitation and equilibrium dialysis method was applied to the separation of bound and unbound drugs. Protein binding reached equilibrium within 12 h of incubation at 37 °C. Liquid-liquid extraction with ethyl acetate was used for sample preparation. The separation was achieved through a Thermo Syncronis C 18 column (50 mm × 2.1 mm, 1.7 μm; Thermo, USA) using gradient elution at a flow rate of 0.4 ml/min. All of the recovery and matrix effect of the method met the requirements of analytical method validation. The plasma protein binding of ( R ) -/ ( S )-HPABA show significant species dependence in enantioselectivity. In addition, the results of molecular docking showed that the combining capacity of ( R ) - HPABA with HSA was higher than that of ( S ) - HPABA. [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 this study, two simple pretreatment methods were comprehensively evaluated for the determination of 135 pesticide residues in roots and rhizomes of Chinese herbal medicines (CHMs). The studied methodologies are (a) solid-phase extraction (SPE) and (b) Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS). For SPE, extraction solvents, SPE cartridges and types and volume of eluent were accessed and optimized. For QuEChERS, different versions, acetic acid concentration and dispersive solid-phase extraction (dSPE) sorbent materials were tested. SPE and QuEChERS were estimated in recovery range, the number of pesticides that were recovered ranging from 90% to 110% and expenses in Corydalis Rhizoma, Chuanxiong Rhizoma and Angelicae Sinensis Radix. QuEChERS method showed better performance than SPE. The method showed good linearity over the range assayed 0.9986–0.9999 (1–80 ng/mL for 124 pesticides, 1–50 ng/mL for 10 pesticides, 1–20 ng/mL for satisfar). The matrix effect was compensated by matrix-based calibration curves with internal standard. The average recoveries of all pesticides were ranging from 70% to 120% at three levels of 10, 50 and 100 ng/g with relative standard deviations less than 20%. The limits of quantification of the 135 pesticides in three matrices were 1–5 ng/g, which were below the maximum residue levels (MRLs) established by the European Union. The verified QuEChERS method was successfully applied to the analysis of 65 actual samples from eight different types of roots and rhizomes of CHMs. Angelicae Sinensis Radix was the most susceptible to pesticides among these samples, and the most frequently detected pesticide was carbendazim with levels below MRLs. Metalaxyl, phorate, atrazine, diniconazole, coumaphos and paclobutrazol were also detected in some samples. [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]

• A rapid UHPLC-MS/MS method for the screening of 16 tryptamines in hair is reported. • LODs ranged between 0.1 and 20 pg/mg and LLOQs ranged from 3 to 50 pg/mg. • The method was applied to 191 hair samples, 77 of which were 5-MeO-DiPT-positive. • 5-MeO-DiPT was determined to be the main tryptamine of abuse found in hair samples. • Most users were aged between 30 and 35. Tryptamines are hallucinogenic substances many of which have appeared recently as novel psychoactive substances (NPS). Herein, we describe the establishment of a rapid UHPLC-MS/MS quantitative method for the targeted screening of 16 tryptamines of abuse in hair. Twenty milligram pieces of hair were pulverized below 4 °C in 0.5 mL of deionized water containing 0.1% formic acid and an internal standard (2 ng/mL psilocin-d 10 and psilocybin-d 4). After subsequent centrifugation, 5 μL of the supernatant was injected into a LC–MS/MS system fitted with a Waters Acquity UPLC HSS T 3 column (100 mm × 2.1 mm, 1.8 μm). The column was gradient eluted at 0.3 mL/min with mobile phases composed of 20 mmol/L ammonium acetate, 5% acetonitrile, and 0.1% formic acid in water (solvent A) and acetonitrile (solvent B). Limits of detection ranged between 0.1 and 20 pg/mg, with limits of quantitation ranging from 3 to 50 pg/mg. The calibration curves for all analytes were linear (r > 0.992). Accuracies varied between 91% and 114%, with intraday precision RSDs < 14% and interday precision RSDs of between 1.3% and 14%. The recoveries of all tryptamines were in the 85–115% range, with the matrix effect ranging from 95% to 112%. The validated method was successfully used to analyse 191 hair samples from suspected tryptamine users, 77 of which were 5-MeO-DiPT-positive, while the 16 tryptamines and their metabolites were not detected in the remaining 114 hair samples. 5-MeO-DiPT and its 5-MeO-NiPT, 5-OH-DiPT, and 4-OH-DiPT metabolites were concurrently detected in 34 hair samples. 5-MeO-DiPT, as the parent drug, was the parent substance found in the hair samples. [ABSTRACT FROM AUTHOR]