Pharmacokinetic and Bioequivalence Study of Lisinopril/Hydrochlorothiazide Tablet Under Fasting and Postprandial Conditions in Healthy Chinese Subjects.

The objective of this research was to evaluate and compare the pharmacokinetic profiles and safety of lisinopril/hydrochlorothiazide (10 mg/12.5 mg) tablets in the test and reference formulations administered to participants in both fasting and postprandial states and to evaluate the bioequivalence of the 2 products in healthy Chinese volunteers. This study employed a single-center, randomized, open-label, single-dose dosing trial involving a cumulative 96 healthy adult participants (60 in the fasting group and 36 in the postprandial group). Each group comprised 2 sequence sets, and a 2-week washout period was implemented. There were no statistically significant differences in time to maximum concentration and terminal elimination half-life between the test and control groups under fasting and postprandial conditions (P > .05), and the 90% CIs for area under the plasma concentration-time curve and maximum plasma concentration were within the bioequivalence range of 80%-125%. Pharmacokinetic results indicate a large food effect for lisinopril, meaning that there is a loss of approximately 20%-25% of systemic exposure from fasting to postprandial administration for both preparations. The study demonstrated that a single oral dose of generic lisinopril/hydrochlorothiazide is bioequivalent to the reference product and well tolerated, with no significant adverse events observed, and that both products are similarly safe in a cohort of healthy Chinese male and female participants, following administration under fasting and postprandial conditions.

Pharmacokinetic and Bioequivalent Study of Potassium Chloride Sustained-Release Tablet Under Different Dietary Conditions in Healthy Chinese Subjects.

Potassium (K+ ) is an endogenous substance that is an essential dietary component. However, the interaction between dietary arrangements and specific effects of dietary K+ intake in bioequivalence studies remains unclear. To investigate the influence of dietary arrangement on the bioequivalence of potassium chloride (KCl) sustained-release tablets in healthy Chinese volunteers, the pharmacokinetics of KCl were compared in two open-label, single-center, randomized, two-period crossover studies with different dietary conditions. All volunteers received an oral dose of 6 g of KCl sustained-release tablets under fasting conditions, with different dietary arrangements. Urine samples were collected on baseline days and 48 hours after tablet consumption. Inductively coupled plasma-optical emission spectrometry was used to measure the concentration of K+ in the urine samples. Pharmacokinetic parameters were analyzed using Phoenix WinNonlin software in a noncompartmental model. In either clinical trial, no significant differences were observed in the maximal rate of urinary excretion and cumulative urinary excretion from 0 to 24 hours of K+ between the reference and test drugs. The bioequivalence studies of both KCl sustained-release tablet formulations were successfully conducted under different dietary conditions.

Simultaneous blockage of contextual TGF-ß by cyto-pharmaceuticals to suppress breast cancer metastasis.

It remains challenging to treat tumor metastasis currently in the light of multiple cascade processes of tumor metastasis. Additionally, multiple clinical drugs for metastasis have quite limited therapeutic potential and even facilitate metastasis in preclinical models. Thus, potential metastasis targets and novel metastasis-directed drugs are urgently needed to be further developed. Herein, transforming growth factor-ß (TGF-ß) is verified to contribute to lung metastasis in a context-dependent manner in the 4T1 orthotopic tumor-bearing mice model, which induces epithelial-mesenchymal-transition (EMT) to promote tumor dissemination from the primary site and dampens the anti-tumor response of neutrophils to support tumor colonization at the metastatic niche. In view of neutrophils' superior tropism towards both inflammatory primary tumor and metastatic niche, SB525334, a TGF-ß receptor inhibitor, is loaded into cationic liposome (SBLP) which is subsequently incorporated into neutrophils to yield the cyto-pharmaceuticals (SBLP/NE). The systemically infused SBLP/NE can simultaneously migrate into both primary and metastatic sites, then release SB525334 in response to tumor stimuli, and contextually inhibit TGF-ß-mediated-EMT and phenotype reversal of infiltrated neutrophils, showing substantial metastasis suppression efficacy without causing any detectable toxicities. This project shifts the paradigm for metastasis suppression therapy by simultaneous blockage of contextual TGF-ß using metastatic-cascades-targeting neutrophil cyto-pharmaceuticals.

Identification and Field Evaluation of the Sex Pheromone of Orthaga achatina (Lepidoptera: Pyralidae).

Orthaga achatina (Lepidoptera: Pyralidae) is the most serious pest in south China of camphor trees, Cinnamomum camphora (L.) Presl, an important urban tree species. Gas chromatography-electroantennographic detection (GC-EAD) of the sex pheromone of O. achatina showed three EAD-active components. Coupled gas chromatography/mass spectrometry analyses identified these as (Z)-11-hexadecenol (Z11-16:OH), (Z)-11-hexadecenyl acetate (Z11-16:OAc), and (3Z,6Z,9Z,12Z,15Z)-tricosapentaene (Z3,Z6,Z9,Z12,Z15-23:H). In field tests using different combinations of the three compounds, male moths were attracted to a mixture of Z11-16:OAc and Z3,Z6,Z9,Z12,Z15-23:H, but less attracted to other blends. Further field tests with different ratios of the two compounds determined the optimal ratio of the binary blend as 500:250. The addition of Z11-16:OH to Z11-16:OAc, or to the binary mixture of Z11-16: OAc and the pentaene did not yield higher catches. This shows that O. achatina uses a mixture of Type I and Type II sex pheromone components. Orthaga achatina is the third Pyraloidea species found to utilize Z3,Z6,Z9,Z12,Z15-23:H as a sex pheromone component.

[Dictamni Cortex powder-induced liver injury based on integrated evidence chain].

A typical clinical case of taking Dictamni Cortex(Baixianpi) powder was analyzed to study liver damage caused by Dictamni Cortex. Liver damage was diagnosed according to the integrated evidence chain method recommended by the Guideline for Diagnosis and Treatment of Herb-Induced Liver Injury. By analyzing clinical history and biochemistry and imaging examinations, underlying diseases, such as viral hepatitis, autoimmune liver disease and alcoholic liver disease, were excluded. Through the investigation of medication history, we made it clear that the patient only took Dictamni Cortex powder during the period, and thus suspected that the liver injury was induced by Dictamni Cortex. Furthermore, the quality of the drug was tested, and the results showed it was consistent with the quality standard of Chinese Pharmacopoeia. DNA barcoding showed that the drug was 100% similar with Dictamnus dasycarpus. Moreover, exogenous harmful substances and chemical drug additions were tested, and the results showed that the content of heavy metal, pesticide residues and microbial toxin were consistent with the required standards, and no chemical drug additions were found in Agilent Fake TCM-Drugs database. In summary, we confirmed that the clinical case of drug-induced liver injury was induced by D. dasycarpus with the dose of 15 g•d⁻¹, which exceeded the prescribed amount of Chinese Pharmacopoeia. According to the Guideline for Diagnosis and Treatment of Herb-Induced Liver Injury, the case of drug-induced liver injury induced by D. dasycarpus was confirmed, which provided a direct and reliable evidence for the study of risk of liver injury induced by D. dasycarpus and its relevant preparations.

T cell--associated immunoregulation and antiviral effect of oxymatrine in hydrodynamic injection HBV mouse model.

Although oxymatrine (OMT) has been shown to directly inhibit the replication of hepatitis B virus (HBV) in vitro, limited research has been done with this drug in vivo. In the present study, the antiviral effect of OMT was investigated in an immunocompetent mouse model of chronic HBV infection. The infection was achieved by tail vein injection of a large volume of DNA solution. OMT (2.2, 6.7 and 20 mg/kg) was administered by daily intraperitoneal injection for 6 weeks. The efficacy of OMT was evaluated by the levels of HBV DNA, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B core antigen (HBcAg). The immunoregulatory activity of OMT was evaluated by serum ELISA and flow cytometry. Results shows that OMT at 20 mg/kg inhibited HBV replication, and it was more efficient than entecavir (ETV) in the elimination of serum HBsAg and intrahepatic HBcAg. In addition, OMT accelerated the production of interferon-γ (IFN-γ) in a dose-dependent manner in CD4+ T cells. Our findings demonstrate the beneficial effects of OMT on the enhancement of immunological function and in the control of HBV antigens. The findings suggest this drug to be a good antiviral therapeutic candidate for the treatment of HBV infection.

Sophocarpine Protects Mice from ConA-Induced Hepatitis via Inhibition of the IFN-Gamma/STAT1 Pathway.

Sophocarpine is the major pharmacologically active compound of the traditional Chinese herbal medicine Radix Sophorae Subprostratae which has been used in treating hepatitis for years in China. It has been demonstrated that Sophocarpine exerts an activity in immune modulation and significantly decreases the production of inflammatory cytokines. However, the protective effects of Sophocarpine in T cell-dependent immune hepatitis remained unknown. The aim of this study was to determine the protective effects and pharmacological mechanisms of Sophocarpine on Concanavalin A (ConA)-induced hepatitis, an experimental model of T cell-mediated liver injury. BALB/C mice were pretreated with Sophocarpine or Bicyclol for five consecutive days. Thirty minutes after the final administration, the mice were injected with 15 mg⋅kg-1 of ConA intravenously. The results indicated that pretreatment with Sophocarpine significantly ameliorated liver inflammation and injury as evidenced by both biochemical and histopathological observations. Moreover, in Sophocarpine-pretreated mice, liver messenger RNA expression levels of chemokines and adhesion molecules, such as macrophage inflammatory protein-1α, CXC chemokine ligand 10, and Intercellular adhesion molecule-1, were markedly reduced. Further studies revealed that Sophocarpine significantly downregulated the expression of T-bet via inhibition of signal transducers and activators of transcription1 (STAT1) activation and overexpression of suppressor of cytokine signaling1, inhibiting the activation of Th1 cells and the expression of Interferon-γ (IFN-γ). Altogether, these results suggest new opportunities to use Sophocarpine in the treatment of T cell-mediated liver disease. In summary, Sophocarpine could attenuate ConA-induced liver injury, and the protective effect of Sophocarpine was associated with its inhibition effect of pro-inflammatory cytokines, chemokines, and the IFN-γ/STAT1 signaling pathway.

Effects of portable solar water quality control machines on aquaculture ponds.

The effects of a portable solar water quality control machine (PSWM) on water quality and sediment of aquaculture ponds were studied in bream aquaculture ponds in Shanghai, China. PSWM operation reduced the temperature and dissolved oxygen (DO) differences between upper and lower water levels. Concentrations of NH4+-N, NO2--N, TN, TP, COD and TSS increased rapidly and reached maximums at 12 h. The density and biomass of phytoplankton and levels of chlorophyll a reached maximums after 40 h of PSWM operation. In a 165-day study, the mean concentrations of NH4+-N, NO2--N and the available phosphorous (AP) in the PSWM ponds were significantly lower than in the control ponds, but the TP was significantly greater than the control ponds. Compared with the test began, the thickness of the sediment in PSWM ponds declined by 12.4 ± 4.3 cm, the control ponds increased by 5.0 ± 2.3 cm and the TN and AP levels in sediment significantly declined. PSWM treatment increased the production of bream and silver carp by 30 and 25%, respectively, and the feed coefficient was reduced by 24.2%. Use of PSWM in bream aquaculture ponds improved water quality, reduced sediment, reduced aquaculture pollution emissions and increased production.

Muscle loading in exoskeletal orthotic use in an activity of daily living.

Strokes are the leading cause of major adult disability with up to 85% of U.S. survivors experiencing hemiparesis. Physical characteristics of upper-extremity exoskeletal orthotics, used in stroke rehabilitation, were evaluated in terms of performance of activities of daily living (ADL), perceived exertion, and muscle load. Simulated orthotic weight distributions, with total extremity loads of 0.81 kg, 1.25 kg and 2.27 kg, were evaluated along with a 0 kg control condition. Response measures included average shoulder/elbow muscle surface electromyography (sEMG) signal amplitude, quality of task completion and total rest time during performance, and Borg CR-10 scale ratings. Device weight distribution, or imposed shoulder moment, was found to have a significant effect on biceps brachii and anterior deltoid activation levels, percent task completion, total rest time, and perceived exertion ratings. Results suggest that heavier upper-extremity orthotics could cause undesirable effects in terms of muscle loading, performance and exertion; such adverse effects could potentially lead to lack of use during patient's rehabilitation.

Association between abnormal default mode network activity and suicidality in depressed adolescents.

BACKGROUND: Suicide is the second leading cause of death among 15- to 29-year-olds in China, and 60 % of suicidal patients have a history of depression. Previous brain imaging studies have shown that depression and suicide may be associated with abnormal activity in default mode network (DMN) regions. However, no study has specifically investigated the relationship between DMN functional activity and suicidal behavior in depressed individuals. Therefore, in the present study, we directly investigated features of DMN brain activity in adolescent patients with histories of depression and attempted suicide. METHODS: A total of 35 sex- and age-matched suicidal depressed patients were compared with 18 non-suicidal depressed patients and 47 healthy controls. We explored functional activity changes in DMN regions that could be associated with suicidal behavior by comparing resting-state functional magnetic resonance imaging (rs-fMRI) signals using independent component analysis (ICA). Scores on six clinical scales that measure depression severity (Hamilton Depression Scale (HDRS) and Beck Depression Inventory (BDI)) and suicidal traits (Barratt Impulsiveness Scale (BIS-11), Suicide Attitude Questionnaire (SAQ), Beck Hopelessness Scale (BHS), and Scale for Suicide Ideation (SSI)) were compared in the three groups. RESULTS: Compared with the healthy controls, all of the evaluated depressed patients showed increased functional connectivity in select DMN regions. The suicidal patients showed increased connectivity in the left cerebellum and decreased connectivity in the right posterior cingulate cortex (PCC), whereas the non-suicidal depressed patients showed increased connectivity in the left superior frontal gyrus, left lingual gyrus and right precuneus and decreased connectivity in the left cerebellum. Compared to the non-suicidal patients, the suicidal patients showed increased connectivity in the left cerebellum and the left lingual gyrus and decreased connectivity in the right precuneus. No differences in the scores of any clinical scales were found between the suicidal and non-suicidal depressed patients. CONCLUSIONS: Collectively, our results highlight the importance of the DMN in the pathophysiology of depression and suggest that suicidal behavior in depressed adolescents may be related to abnormal functional connectivity in the DMN. In particular, abnormal connectivity in the PCC/precuneus and left cerebellum might be a predictor of suicidal behavior in depressed adolescent patients.

Design and Application of a Solar Mobile Pond Aquaculture Water Quality-Regulation Machine Based in Bream Pond Aquaculture.

Bream pond aquaculture plays a very important role in China's aquaculture industry and is the main source of aquatic products. To regulate and control pond water quality and sediment, a movable solar pond aquaculture water quality regulation machine (SMWM) was designed and used. This machine is solar-powered and moves on water, and its primary components are a solar power supply device, a sediment lifting device, a mechanism for walking on the water's surface and a control system. The solar power supply device provides power for the machine, and the water walking mechanism drives the machine's motion on the water. The sediment lifting device orbits the main section of the machine and affects a large area of the pond. Tests of the machine's mechanical properties revealed that the minimum illumination necessary for the SMWM to function is 13,000 Lx and that its stable speed on the water is 0.02-0.03 m/s. For an illumination of 13,000-52,500 Lx, the sediment lifting device runs at 0.13-0.35 m/s, and its water delivery capacity is 110-208 m(3)/h. The sediment lifting device is able to fold away, and the angle of the suction chamber can be adjusted, making the machine work well in ponds at different water depths from 0.5 m to 2 m. The optimal distance from the sediment lifting device to the bottom of the pond is 10-15 cm. In addition, adjusting the length of the connecting rod and the direction of the traction rope allows the SMWM to work in a pond water area greater than 80%. The analysis of water quality in Wuchang bream (Parabramis pekinensis) and silver carp (Hypophthalmichthys molitrix) culture ponds using the SMWM resulted in decreased NH3(+)-N and available phosphorus concentrations and increased TP concentrations. The TN content and the amount of available phosphorus in the sediment were reduced. In addition, the fish production showed that the SMWM enhanced the yields of Wuchang bream and silver carp by more than 30% and 24%, respectively. These results indicate that the SMWM may be suitable for Wuchang bream pond aquaculture in China and that it can be used in pond aquaculture for regulating and controlling water quality.

Attentional bias in adults with cannabis use disorders.

There has been modest examination of attentional bias in individuals with cannabis use disorders. Clinical implications of this work are directly relevant to better informing extant evidence-based treatment for substance use disorders (e.g., relapse prevention) and/or developing novel interventions. The overarching aim of this investigation was to examine a novel attentional bias task in adults with cannabis use disorders. Participants were comprised of 25 adults (8 women: M age = 31, SD = 6.8; range = 22-45) with cannabis use disorders (n = 12) and controls (n = 13) without any current (past month) psychopathology. Relative to controls, adults with cannabis use disorders had greater attentional bias scores. These differences were present only at the 125-ms probe time, where the cannabis use disorders group showed greater attentional bias to cannabis cues than the control group (adjusted p = .001, cannabis use disorders mean = 59.9, control mean = -24.8, Cohen's d-effect size for 125 ms = 1.03). The cannabis use disorders group also reported significantly greater perceived stress and post-task stress scores than the control group, but stress was not related to attentional bias. This study informs understanding of the influence of cannabis cues on visual detection and reaction time under different cue-target onset times, as attentional bias was most prevalent under time pressure to detect the probe.

Two esterases from the genus Spodoptera degrade sex pheromones and plant volatiles.

In moths, high temporal sensitivity in perception of sex pheromones and host plant volatiles suggests the existence of mechanisms acting to maintain antennal sensitivity. The antennal enzymes have been long hypothesized to play a central role in the mechanisms, by rapid metabolism of the odorants soon after the fulfillment of the sensillum receptor activation. In the present study, two putative homologous esterases, SexiCXE13 and SlituCXE13, were cloned by RT-PCR and RACE procedures from Spodoptera exigua and Spodoptera litura, respectively. The phylogenetic tree assigned the two genes into the same group with two previously identified male antennal-specific pheromone-degrading enzymes. SexiCXE13 and SlituCXE13 were expressed in High Five cells, and the enzymatic characteristics and substrate specificity were investigated using the purified recombinant enzymes. Both esterases showed high activity to a variety of acetate substrates, including the sex pheromones, their analogs, and some common plant odorants. Our study, for the first time, provides direct biochemical and molecular evidence that the ubiquitously expressed enzyme has the ability to degrade sex pheromones and plant volatiles, and thus this adds new knowledge to the mechanism underlying the sensitivity of moth olfaction.

The influence of dopamine ß-hydroxylase gene polymorphism rs1611115 on levodopa/carbidopa treatment for cocaine dependence: a preliminary study.

Recent studies have suggested that heterogeneity in the level of dopamine activity and function might be useful for identifying a subgroup of cocaine-dependent patients responding better to dopamine-enhancement pharmacotherapy. Here we hypothesized that response to levodopa/carbidopa treatment would be greater in patients with genetically determined low levels of the dopamine metabolizing enzyme dopamine ß-hydroxylase (DßH). Seventy-one cocaine-dependent patients who participated in a 12-week randomized double-blind placebo-controlled trial of levodopa/carbidopa were genotyped for the DßH gene (DBH) polymorphism rs1611115. Our results showed that for patients with the low DßH activity genotypes (CT/TT) who received levodopa, the odds of having cocaine-positive urine decreased significantly over treatment compared with placebo-treated patients with the CT/TT genotypes (P=0.004). Individuals with the normal DßH activity genotype (CC) showed no differential response to levodopa. These preliminary results need to be confirmed in a larger sample focusing on the DBH polymorphism.

Effects of escitalopram on attentional bias to cocaine-related stimuli and inhibitory control in cocaine-dependent subjects.

Key characteristics of cocaine dependence include attentional bias to cocaine cues and impaired inhibitory control. Studies suggest that serotonin modulates both cocaine cue reactivity and inhibitory control. We investigated effects of the selective serotonin reuptake inhibitor escitalopram on cocaine cue reactivity and inhibitory processes in cocaine-dependent subjects. In a double-blind placebo-controlled design, cocaine-dependent subjects received placebo (n=12) or escitalopram (n=11; 10 mg on days 1-3, 20 mg on days 4-24 and 10 mg on days 25-28) orally, once daily for 4 weeks. The cocaine Stroop and immediate memory task (IMT) were administered at baseline, days 1, 4, 11, 18 and 25 after placebo or escitalopram initiation. There were no significant between-group differences in baseline performance on the cocaine Stroop task or the IMT. On day 1 (acute phase), escitalopram produced a significantly greater decrease from baseline than placebo in attentional bias measured by cocaine Stroop task 5 hours post-dose. No significant changes from baseline in attentional bias were observed on subsequent test days (chronic phase). Inhibitory control as measured by IMT commission error rate was not significantly different between two groups in either the acute or chronic phase. Consistent with preclinical data, serotonin-modulating drugs like escitalopram may have acute effects on cocaine cue reactivity in human cocaine users.

[Significance of low molecular weight urinary protein for assessment of early renal damage in patients with multiple myeloma].

This study was purposed to evaluate the clinical significance of low molecular weight urinary proteins for diagnosis of early renal damage in patients with multiple myeloma (MM). Medical records of 278 patients with MM in Nanjing School of Clinical Medicine from January 2004 to May 2012 were analyzed retrospectively. These patients were divided into 3 groups: glomerular damage group (n = 143), tubular damage group (n = 114) and normal group (n = 21). The clinical and laboratorial data were compared among them. The correlations of urinary retinol-binding protein (RBP) or urinary N-acetyl-ß-D-amino-glucosaminidase (NAG) with blood urea nitrogen (BUN), Scr, blood cystatin-C (Cys-C), clearance of creatinine (Ccr), 24 h protein uria and 24 h urine light chains were further analyzed, and the correlation of renal tubulointerstitial lesion scores with low molecular weight urinary proteins in 61 patients were also analyzed. The area under curve (ROC curve) was used to evaluate and compare the discrimination of urinary RBP and urinary NAG. The results showed that glomerular damage group had higher urinary RBP than tubular damage group. However, glomerular damage group had lower urinary NAG than tubular damage group. The two groups had higher urinary RBP and urinary NAG than that in normal group. Urinary RBP related positively to the level of Scr, BUN, Cys-C, 24 h proteinurias and related negatively to the level of Ccr. Urinary NAG related positively to the level of 24 h proteinurias, Ccr and related negatively to the level of Cys-C. Renal tubulointerstitial lesions were significantly correlated with urinary RBP, but weakly correlated with urinary NAG. It is concluded that urinary RBP significantly correlates with renal tubular damage. Compared with urinary NAG, urinary RBP can better assess the extent of renal damage, and has higher specificity.

Paeoniflorin protects against ANIT-induced cholestasis by ameliorating oxidative stress in rats.

Paeoniflorin, one of the primary bioactive components in Chi shao, are widely used in traditional Chinese medicine. A lot of evidences suggest that Paeoniflorin has potential anti-oxidant effects. However, whether Paeoniflorin plays roles in cholestasis is unclear. In this study, we examined the protective effect of Paeoniforin against alpha-naphthylisothicaynate (ANIT)-induced cholestasis in rats. Our data demonstrated that the high (0.2 g/kg body weight) and medium (0.1 g/kg body weight) doses of Paeoniflorin significantly prevented ANIT-induced changes in bile flow and the serum levels of total bilirubin, direct bilirubin, total bile acid, γ-glutamyltranspeptidase, glutamate-pyruvate transaminase, glutamate-oxaloacetic transaminase and alkaline phosphatase. Moreover, we also found that Paeoniflorin significantly inhibited nitric oxide and malondialdehyde production, and restored glutathione decrease induced by ANIT. EPR data further indicated that Paeoniflorin inhibited ANIT-mediated reactive oxygen species (ROS) production. The overexpression of NADPH oxidase 4 induced by ANIT were significantly reversed when treated with Paeoniflorin, suggesting that Paeoniflorin could scavenge ROS via inhibiting NADPH oxidase 4 expression. Paeoniflorin treatment could also relieve ANIT-induced liver pathological injuries as indicated by histological assay. These findings indicate that Paeoniflorin exerts a dose-dependent protective effect on ANIT-induced cholestatic liver injury in rats, and the mechanism of this activity is related to its attenuation of oxidative stress in liver tissue.

[Diagnostic value of renal function parameter detection of early renal damage in multiple myeloma].

Renal damage is one of the most common complications and cause of death in patients with multiple myeloma (MM). The studies have pointed out that early renal impairment is risk factor for progress of this disease, timely diagnosis and prompt intervention therapy are very important to improve the prognosis and survival of MM patients. Therefore, the diagnosis of early renal damage is crucial for clinical treatment. The progress on detection of early renal damage parameters and their value are reviewed in this article.

Influence of nonpolar substances on the extraction efficiency of six alkaloids in Zoagumhwan investigated by ultra performance liquid chromatography and photodiode array detection.

A reverse phase ultra performance liquid chromatography and photodiode array (UPLC-PDA) detection method was established for the determination of six alkaloids in Zoagumhwan (ZGW), and further for investigating the influence of nonpolar substances on the extraction efficiency of these alkaloids. The method was based on a BEH C(18) (50 mm × 2.1 mm, 1.7 µm) column and mobile phase of aqueous phosphoric acid and acetonitrile including 0.05% buffer solution under gradient elution. ZGW samples of ZGW I, II, III and IV were obtained and prepared by pre-processing the crude materials of Coptidis rhizoma and Evodiae fructus using four technologies, namely direct water decoction, removal of nonpolar substances in Evodiae fructus by supercritical fluid extraction (SFE), removal of nonpolar substances in ZGW by SFE and removal of nonpolar substances in ZGW by steam distillation. The developed and validated UPLC-PDA method was precise, accurate and sensitive enough based on the facts that the six alkaloids showed good regression (r > 0.9998), the limit of detections and quantifications for six alkaloids were less than 28.8 and 94.5 ng/mL, respectively, and the recovery was in the range of 98.56%-103.24%. The sequence of the total contents of six alkaloids in these samples was ZGW II > ZGW IV > ZGW III > ZGW I. ZGW II, in which nonpolar substances, including essential oils, were firstly removed from Evodiae fructus by SFE, had the highest content of the total alkaloids, indicating that extraction efficiency of the total alkaloids could be remarkably increased after Evodiae fructus being extracted by SFE.