Pharmacokinetics of IMM-H012 in rats using ultra-performance liquid chromatography-tandem mass spectrometry.

The present study examined the pharmacokinetics of IMM-H012 in rat plasma, utilizing ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Internal standard cilostazol was employed, and plasma samples were processed using acetonitrile precipitation. A mobile phase (acetonitrile-0.1% formic acid in water) with gradient elution was used to achieve chromatographic separation using a UPLC BEH C18 column. In multiple reaction monitoring mode, electrospray ionization MS/MS was utilized in positive ionization mode. Based on findings, the lower limit of quantification was 2 ng/mL, and the linearity of IMM-H012 in rat plasma was found to be acceptable within the range of 2-2000 ng/mL (R2 > 0.995). The intra-day and inter-day precision relative standard deviation was less than 14% of IMM-H012 in rat plasma. The matrix effect was within the range of 102%-107%, and the accuracy ranged from 92% to 113%. Pharmacokinetics of IMM-H012 in rats after oral administration were successfully studied using UPLC-MS/MS.

Development of an ultra-high-performance liquid chromatography-tandem mass spectrometry method for the simultaneous determination of crassicauline A, fuziline, karacoline, and songorine in rat plasma and application in their pharmacokinetics.

In this paper, an ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for quantifying the levels of crassicauline A, fuziline, karacoline, and songorine in rat plasma. After processing the rat plasma, the proteins in the plasma were separated by extracting the analytes with acetonitrile-methanol (9:1, v/v). The chromatographic column used was the UPLC HSS T3 column, and the mobile phase (methanol-water with 0.1% formic acid) under a gradient elution profile was used to separate the four compounds, with elution times for each analyte being less than 5 min. Electrospray ionization in positive-ion mode and operating in multiple reaction monitoring mode was used for quantitative analysis. Crassicauline A, fuziline, karacoline, and songorine were administered to 48 rats (n = 6 per group) orally (5 mg/kg) and intravenously (0.5 mg/kg). The standard curves demonstrated excellent linearity in the range of 1-2500 ng/mL, wherein all r values were greater than 0.99. The UPLC-MS/MS method for the determination of crassicauline A, fuziline, karacoline, and songorine in rat plasma was successfully applied in determining their pharmacokinetics parameters, from which their oral bioavailabilities were calculated to be 18.7%, 4.3%, 6.0%, and 8.4%, respectively.

Abnormalities of serum lipid metabolism in patients with acute paraquat poisoning caused by ferroptosis.

As the mechanism of paraquat (PQ) poisoning is still not fully elucidated, and no specific treatment has been developed in medical practice, the management of PQ poisoning continues to present a medical challenge. In this study, the objective was to investigate the early metabolic changes in serum metabolism and identify the key metabolic pathways involved in patients with PQ poisoning. Quantitative analysis was conducted to determine the relevant metabolites. Additionally, experiments were carried out in both plasma and cell to elucidate the mechanisms underlying metabolic disorder and cell death in PQ poisoning. The study found that polyunsaturated fatty acids (PUFAs) and their metabolites, such as arachidonic acid (AA) and hydroxy eicosatetraenoic acids (HETEs), were significantly increased by non-enzymatic oxidative reaction. Reactive oxygen species (ROS) production increased rapidly at 2 h after PQ poisoning, followed by an increase in PUFAs at 12 h, and intracellular glutathione, cysteine (Cys), and Fe2+ at 24 h. However, at 36 h later, intracellular glutathione and Cys decreased, HETEs increased, and the expression of SLC7A11 and glutathione peroxidase 4 (GPX4) decreased. Ultrastructural examination revealed the absence of mitochondrial cristae. Deferoxamine was found to alleviate lipid oxidation, and increase the viability of PQ toxic cells in the low dose. In conclusion, unsaturated fatty acids metabolism was the key metabolic pathways in PQ poisoning. PQ caused cell death through the induction of ferroptosis. Inhibition of ferroptosis could be a novel strategy for the treatment of PQ poisoning.

Determination of isoscoparin in mouse blood using UPLC-MS/MS and its pharmacokinetics.

This study developed a UPLC-MS/MS method to detect isoscoparin in mouse blood, determined the pharmacokinetics of isoscoparin in mice after intravenous (5 mg/kg) and intragastric (20 mg/kg) administration, and calculated the absolute bioavailability. A HSS T3 column was used for separation, and the column temperature was set at 40°C. The mobile phases were acetonitrile and 0.1% formic acid, and the gradient elution procedure was used. The blood sample was treated with protein precipitant with acetonitrile-methanol (9:1, v/v). Multiple reaction monitoring mode was used for quantitative analysis in electrospray positive-ion mode. It showed a good linear relationship in the range of 1-4000 ng/mL (r > 0.998); the intra-day and inter-day precision was <12%, and the accuracy was 86-112%. The recovery was >68%, and the matrix effect was 86-90%. The half-life of isoscoparin was relatively short in mice, and the bioavailability was 2.6%. The developed UPLC-MS/MS method was rapid, sensitive, and suitable for the pharmacokinetics of isoscoparin in mice.

A practical way to enhance the synthesis of N8- from an N3- precursor, studied by both computational and experimental methods.

Polymeric nitrogen (PN) belongs to a general family of materials containing all-nitrogen molecules or clusters. Although it is rare and challenging to synthesize PN members, they are attracting increasing scientific attention due to their high energy storage capacity and possible use as a green catalyst. A few theoretical calculations predicted the possible PN phases from N2 gas, but they all require extremely high pressures and temperatures to synthesize. In this work, a practical way to synthesize N8 polymeric nitrogen from an N3- precursor is elucidated using density functional theory calculations. The detailed mechanism, , is determined. The calculated energy barriers indicate that the first step is the rate-limiting step. This result guides us to rationally synthesize N8 under UV (254 nm) irradiation, chosen based on the calculated absorption spectrum for the azide anion. As expected, UV irradiation enhances N8 yields by nearly four times. This provides an interesting route to the scalable synthesis of high energy density N8 compounds.

Metabolic and transcriptional changes in seminal plasma of asthenozoospermia patients.

This study was designed to investigate the metabolic and transcriptional alterations in seminal fluid caused by asthenozoospermia (AS). To address these issues, a method of metabonomics based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and real-time quantitative PCR (RT-qPCR) was performed to identify some crucial biomarkers and transcription levels of the enzymes in seminal fluid. Seminal fluid samples were collected from 87 AS patients and 73 healthy males with normozoospermia. The quantitative analysis by UPLC-MS/MS showed that 19 metabolites in seminal plasma were associated with AS, and they were involved in several metabolic pathways, such as energy metabolism, purine metabolism, methionine cycle, and branched chain amino acid metabolism. Among these metabolites, the levels of citric acid, malic acid, succinic acid, and pyruvic acid, which are related to energy metabolism, were collectively reduced in the AS group, whereas the lactic acid level was enhanced. These results indicated that lesser energy source (adenosine triphosphate) was produced through the anaerobic glycolysis pathway rather than via aerobic catabolism of suger and tricarboxylic acid cycle, resulting in reduced power of sperms. Meanwhile, partial least squares discriminant analysis showed significant differences in metabolic profiles between the AS and control groups. In addition, RT-qPCR results revealed that the expression levels of four genes encoding fructokinase citrate synthase, succinate dehydrogenase, and spermine synthase, which were related to energy metabolism, were decreased in the AS group. The 23 descriptors with differential expression in AS may be valuable for the diagnosis and sequential study on AS. These results will help highlight the role of sperm inactivity in AS pathogenesis.

Metabolomics Analysis in Acute Paraquat Poisoning Patients Based on UPLC-Q-TOF-MS and Machine Learning Approach.

Most paraquat (PQ) poisoned patients died from acute multiple organ failure (MOF) such as lung, kidney, and heart. However, the exact mechanism of intoxication is still unclear. In order to find out the initial toxic mechanism of PQ poisoning, a blood metabolomics study based on ultraperformance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and efficient machine learning approach was performed on 23 PQ poisoned patients and 29 healthy subjects. The initial PQ plasma concentrations of PQ poisoned patients were >1000 ng/mL, and the blood samples were collected at before first hemoperfusion (HP), after first HP, and after last HP. The results showed that PQ poisoned patients all differed from healthy subjects, whatever they were before or after first HP or after last HP. The efficient machine learning approaches selected key metabolites from three UPLC/Q-TOF-MS data sets which had the highest classification performance in terms of classification accuracy, Matthews Correlation Coefficients, sensitivity, and specificity, respectively. The mass identification revealed that the most important metabolite was adenosine, which sustained in low level, regardless of whether PQ poisoned patients received HP treatment. In conclusion, decreased adenosine was the most important metabolite in PQ poisoned patients. The metabolic disturbance caused by PQ poisoning cannot be improved by HP treatment even the PQ was cleared from the blood.

Pharmacokinetics and bioavailability of gelsenicine in mice by UPLC-MS/MS.

Gelsenicine is an indole alkaloid isolated from Gelsemium elegans Benth. In recent years, the role of G. elegans Benth preparations in anti-tumor, analgesic, dilatation and dermatological treatment has attracted attention, and it has been applied clinically, but it is easy to cause poisoning with its use. An UPLC-MS/MS method was established to determine the gelsenicine in mouse blood, and the pharmacokinetics of gelsenicine after intravenous (0.1 mg/kg) and intragastric (0.5 and 1 mg/kg) administration was studied. Deltalin was used as internal standard; a UPLC BEH C18 column was used for chromatographic separation. The mobile phase consisted of acetonitrile and 10 mmol/L ammonium acetate (0.1% formic acid) with a gradient elution flow rate of 0.4 mL/min. Multiple reaction monitoring mode was used for quantitative analysis of gelsenicine in electrospray ionization positive interface. Proteins from mouse blood were removed by acetonitrile precipitation. A validation of this method was performed in accordance with the US Food and Drug Administration guidelines. In the concentration range of 0.05-100 ng/mL, the gelsenicine in the mouse blood was linear (r > 0.995), and the lower limit of quantification was 0.05 ng/mL. In the mouse blood, the intra-day precision RSD was <12%, the inter-day precision RSD was <15%, the accuracy ranged from 89.8 to 112.3%, the average recovery was >76.8%, and the matrix effect was between 103.7 and 108.4%, which meet the pharmacokinetic research requirements of gelsenicine. The UPLC-MS/MS method is sensitive, rapid and selective, and has been successfully applied to the pharmacokinetic study of gelsenicine in mice. The absolute bioavailability of gelsenicine is 1.13%.

Determination of corypalmine in mouse blood by UPLC-MS/MS and its application to a pharmacokinetic study.

In this work, a selective and sensitive ultra-performance liquid chromatography tandem mass spectrometry method was established and validated for determination of corypalmine in mouse blood after oral or intravenous administration. A UPLC BEH C18 column was used to separate corypalmine and berberrubine (internal standard) at 40°C. The mobile phase was composed of acetonitrile and 10 mmol/L ammonium acetate (containing 0.1% formic acid) at a flow rate of 0.4 mL/min, and the total run time was 4.0 min. Electrospray ionization in positive ion mode was applied; target fragment ions m/z 342.2 → 178.0 for corypalmine and m/z 322.1 → 307.0 for berberrubine were identified with multiple reaction monitoring mode. The linear range was 1-1000 ng/mL (r > 0.995) and the lower limit of quantification for corypalmine in plasma was 1.0 ng/mL. The intra- and inter-day precisions were both <14%. The range of accuracy in this method was 97.5-109.0%. Mean recovery was >69.6%, and the matrix effect was 96.8-107.6%. Based on its high sensitivity, specificity and reliability, this method was successfully applied to study the pharmacokinetic parameters of corypalmine in mouse by oral and intravenous administration, and finally, the bioavailability of corypalmine was identified at 4.6%.

Determination of armepavine in mouse blood by UPLC-MS/MS and its application to pharmacokinetic study.

The purpose of this study was to develop an ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method to determine armepavine in mouse blood. Nuciferine was used as internal standard. Chromatographic separation was performed on a UPLC BEH (2.1 × 50 mm, 1.7 µm) column with a gradient elution of acetonitrile and 10 mmol/L ammonium acetate solution (containing 0.1% formic acid). The quantitative analysis was conducted in multiple reaction monitoring mode with m/z 314.1 → 106.9 for armepavine and m/z 296.2 → 265.1 for nuciferine. Calibration curves were linear (r > 0.995) over the concentration range 1-1000 ng/mL in mouse blood with a lowest limit of quantitation of 1 ng/mL. The intra- and inter-day precisions of armepavine in mouse were < 13.5 and 10.8%, respectively. The accuracy ranged between 86.8 and 103.3%. Meanwhile, the average recovery was >70.7% and the matrix effect was within the range 109.5-113.7%. All of the obtained data confirmed the satisfactory sensitivity and selectivity of the developed method which was then successfully applied to evaluate the pharmacokinetic behavior of armepavine in mouse for the first time. The bioavailability of armepavine in mouse was calculated to be 11.3%.

Early Metabolome Profiling and Prognostic Value in Paraquat-Poisoned Patients: Based on Ultraperformance Liquid Chromatography Coupled To Quadrupole Time-of-Flight Mass Spectrometry.

Paraquat (PQ) has caused countless deaths throughout the world. There remains no effective treatment for PQ poisoning. Here we study the blood metabolome of PQ-poisoned patients using ultraperformance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS). Patients were divided into groups according to blood PQ concentration. Healthy subjects served as controls. Metabolic features were statistically analyzed using multivariate pattern-recognition techniques to identify the most important metabolites. Selected metabolites were further compared with a series of clinical indexes to assess the prognostic value. PQ-poisoned patients showed substantial differences compared with healthy subjects. Based on variable of importance in the project (VIP) values and statistical analysis, 17 metabolites were selected and identified. These metabolites well-classified low PQ-poisoned patients, high PQ-poisoned patients, and healthy subjects, which was better than that of a complete blood count (CBC). Among the 17 metabolites, 20:3/18:1-PC (PC), LPA (0:0/16:0) (LPA), 19-oxo-deoxycorticosterone (19-oxo-DOC), and eicosapentaenoic acid (EPA) had prognostic value. In particular, EPA was the most sensitive one. Besides, the levels of EPA was correlated with LPA and 19-oxo-DOC. If EPA was excessively consumed, then prognosis was poor. In conclusion, the serum metabolome is substantially perturbed by PQ poisoning. EPA is the most important biomarker in early PQ poisoning.

Serum metabolic changes in rats after intragastric administration of dextromethorphan.

Dextromethorphan is recognized as a substance of abuse around the world. An estimated 3.1 million people between the ages of 12 and 25 years (5.3%) misused over-the-counter cough and cold medications in 2006. In this study, we developed a serum metabolomic method by gas chromatography-mass spectrometry (GC-MS) to evaluate the effect of abuse of dextromethorphan on rats. The dextromethorphan-treated rats were given 12, 24 and 48 mg/kg (low, medium, high) of dextromethorphan by intragastric administration each day for 3 days. Partial least squares-discriminate analysis revealed that intragastric administration of dextromethorphan induced metabolic perturbations. Compared with the control (healthy) group, the levels of propanoic acid, urea, heptafluorobutanoic acid, 2-hexyldecanoic acid and butanedioic acid of the low group decreased; levels of propanoic acid and heptafluorobutanoic acid of the medium group decreased, while that of benzoic acid increased; and levels of 2-hexyldecanoic acid, glycerol and butanedioic acid of the high group increased. These biomarkers are involved in the citric acid cycle, urea cycle, glycerolipid metabolism and tricarboxylic acid cycle. The results indicate that the metabolomic method by GC-MS may be useful to elucidate abuse of dextromethorphan. According to the pathological changes in the liver at different dosages, dextromethorphan is not hepatotoxic after intragastric administration of 12, 24 and 48 mg/kg for 3 days.

Pharmacokinetic study of ardisiacrispin A in rat plasma after intravenous administration by UPLC-MS/MS.

In this work, a sensitive and selective UPLC-MS/MS method for determination of ardisiacrispin A in rat plasma was developed. Cyasterone used as an internal standard (IS) and protein precipitation by acetonitrile-methanol (9:1, v/v) was used to prepare samples. Chromatographic separation was achieved on a UPLC BEH C18 column (2.1 × 100 mm, 1.7 µm) with 0.1% formic acid and acetonitrile as the mobile phase with gradient elution. An electrospray ionization source was applied and operated in positive ion mode; multiple reaction monitoring mode was used for quantification using target fragment ions m/z 1083.5 → 407.1 for ardisiacrispin A and m/z 521.3 → 485.2 for IS. Calibration plots were linear throughout the range 5-2000 ng/mL for ardisiacrispin A in rat plasma. Mean recoveries of ardisiacrispin A in rat plasma ranged from 80.4 to 92.6%. The values of RSD of intra- and inter-day precision were both <11%. The accuracy of the method was between 97.3 and 105.6%. The method was successfully applied to pharmacokinetic study of ardisiacrispin A after intravenous administration in rats.

Effect of alprazolam on rat serum metabolic profiles.

We developed a serum metabolomic method by gas chromatography-mass spectrometry (GC-MS) to evaluate the effect of alprazolam in rats. The GC-MS with HP-5MS (0.25 µm × 30 m × 0.25 mm) mass was conducted in electron impact ionization (EI) mode with electron energy of 70 eV, and full-scan mode with m/z 50-550. The rats were randomly divided to four groups, three alprazolam-treated groups and a control group. The alprazolam-treated rats were given 5, 10 or 20 mg/kg (low, medium, high) of alprazolam by intragastric administration each day for 14 days. The serum samples were corrected on the seventh and fourteenth days for metabolomic study. The blood was collected for biochemical tests. Then liver and brain were rapidly isolated and immersed for pathological study. Compared with the control group, on the seventh and fourteen days, the levels of d-glucose, 9,12-octadecadienoic acid, butanoic acid, l-proline, d-mannose and malic acid had changed, indicating that alprazolam induced energy metabolism, fatty acid metabolism and amino acid metabolism perturbations in rats. There was no significant difference for alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, urea and uric acid between controls and alprazolam groups. According to the pathological results, alprazolam is not hepatotoxic. Metabolomics could distinguish different alprazolam doses in rats.

Tissue metabolic changes for effects of pirfenidone in rats of acute paraquat poisoning by GC-MS.

We developed a metabolomic method to evaluate the effect of pirfenidone on rats with acute paraquat (PQ) poisoning, through the analysis of various tissues (lung, liver, kidney, and heart), by gas chromatography-mass spectrometry (GC-MS). Thirty-eight rats were randomly divided into a control group, an acute PQ (20 mg kg-1) poisoning group, a pirfenidone (20 mg kg-1) treatment group, and a pirfenidone (40 mg kg-1) treatment group. Partial least squares-discriminate analysis (PLS-DA) revealed metabolic alterations in rat tissue samples from the two pirfenidone treatment groups after acute PQ poisoning. The PLS-DA 3D score chart showed that the rats in the acute PQ poisoning group were clearly distinguished from the rats in the control group. Also, the two pirfenidone treatment groups were distinguished from the acute PQ poisoning group and control group. Additionally, the pirfenidone (40 mg kg-1) treatment group was separated farther than the pirfenidone (20 mg kg-1) treatment group from the acute PQ poisoning group. Evaluation of the pathological changes in the rat tissues revealed that treatment with pirfenidone appeared to decrease pulmonary fibrosis in the acute PQ poisoning rats. The results indicate that pirfenidone induced beneficial metabolic alterations in the tissues of rats with acute PQ poisoning. Rats with acute PQ poisoning exhibited a certain reduction in biochemical indicators after treatment with pirfenidone, indicating that pirfenidone could protect liver and kidney function. Accordingly, the developed metabolomic approach proved to be useful to elucidate the effect of pirfenidone in rats of acute PQ poisoning.

Microanatomy of the brachial plexus roots and its clinical significance.

PURPOSE: To provide the anatomical basis of brachial plexus roots for the diagnosis and treatment of brachial plexus root avulsion injury. METHODS: The morphological features of brachial plexus roots were observed and measured on 15 cervicothoracic spine of adult cadavers. The relationship of brachial plexus nerve roots and the surrounding tissues also were observed, as well as the blood supply of anterior and posterior roots of the brachial plexus. RESULTS: Origination of the nerve roots in the dorsal-ventral direction from the midline was fine-tuned at each level along the spinal cord. The minimum distance of the origin of the nerve root to midline was 2.2 mm at C 5, while the maximum was 3.1 mm at T 1. Inversely, the distance between the origin of the posterior root and the midline of the spinal cord gradually decreased, the maximum being 4.2 mm at C 5 and minimum 2.7 mm at T 1. Meanwhile, there was complicated fibrous connection among posterior roots of the brachial plexus. The C 5-6 nerve roots interlaced with tendons of the scalenus anterior and scalenus medius and fused with the transverse-radicular ligaments in the intervertebral foramina. However, these ligaments were not seen in C 7-8, and T 1. The blood supply of the anterior and posterior roots of the brachial plexus was from the segmental branches of the vertebral artery, deep cervical artery and ascending cervical artery, with a mean outer diameter of 0.61 mm. CONCLUSIONS: The systematic and comprehensive anatomic data of the brachial plexus roots provides the anatomical basis to diagnose and treat the brachial plexus root avulsion injury.

Effect of codeine on CYP450 isoform activity of rats.

CONTEXT: Codeine, also known as 3-methylmorphine, is an opiate used to treat pain, as a cough medicine and for diarrhoea. No study on the effects of codeine on the metabolic capacity of CYP enzyme is reported. OBJECTIVE: In order to investigate the effects of codeine on the metabolic capacity of cytochrome P450 (CYP) enzymes, a cocktail method was employed to evaluate the activities of CYP2B1, CYP2D1, CYP1A2, CYP3A2 and CYP2C11. MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into codeine group (low, medium, high) and control group. The codeine group rats were given 4, 8, 16 mg/kg (low, medium, high) codeine by continuous intragastric administration for 14 days. Five probe drugs bupropion, metroprolol, phenacetin, midazolam and tolbutamide were given to rats through intragastric administration, and the plasma concentrations were determined by UPLC-MS/MS. RESULTS AND CONCLUSION: The pharmacokinetic parameters of bupropion and metroprolol experienced obvious change with AUC(0-t), Cmax increased and CL decreased for bupropion in medium dosage group and midazolam low dosage group. This result indicates that the 14 day-intragastric administration of codeine may inhibit the metabolism of bupropion (CYP2B1) and midazolam (CYP3A2) in rat. Additional, there are no statistical differences for albumin (ALB), alkaline phosphatase (ALP), creatinine (Cr) after 14 intragastric administration of codeine, while alanine aminotransferase (ALT), aspartate aminotransferase (AST), uric acid (UA) increased compared to control group. The biomedical test results show continuous 14 day-intragastric administration of codeine would cause liver damage.

Brain metabolomics in rats after administration of ketamine.

In this study, we developed a brain metabolomic method, based on gas chromatography-mass spectrometry (GC/MS), to evaluate the effect of ketamine on rats. Pattern recognition analysis, including both principal component analysis and partial least squares-discriminate analysis revealed that ketamine induced metabolic perturbations. Compared with the control group, the levels of glycerol, uridine, cholesterol in rat brain of the ketamine group (50 mg/kg, 14 days) decreased, while the urea levels increased. Our results indicate that metabolomic methods based on GC/MS may be useful to elucidate ketamine abuse through the exploration of biomarkers.

Pharmacokinetic study of dendrobine in rat plasma by ultra-performance liquid chromatography tandem mass spectrometry.

Dendrobine, considered as the major active alkaloid compound, has been used for the quality control and discrimination of Dendrobium which is documented in the Chinese Pharmacopoeia. In this work, a sensitive and simple ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for determination of dendrobine in rat plasma is developed. After addition of caulophyline as an internal standard (IS), protein precipitation by acetonitrile-methanol (9:1, v/v) was used to prepare samples. Chromatographic separation was achieved on a UPLC BEH C18 (2.1 ×100 mm, 1.7 µm) column with acetonitrile and 0.1% formic acid as the mobile phase with gradient elution. An electrospray ionization source was applied and operated in positive ion mode; multiple reaction monitoring mode was used for quantification using target fragment ions m/z 264.2 → 70.0 for dendrobine and m/z 205.1 → 58.0 for IS. Calibration plots were linear throughout the range 2-1000 ng/mL for dendrobine in rat plasma. The RSDs of intra-day and inter-day precision were both <13%. The accuracy of the method was between 95.4 and 103.9%. The method was successfully applied to pharmacokinetic study of dendrobine after intravenous administration. Copyright © 2015 John Wiley & Sons, Ltd.

Metabolic changes in rat urine after acute paraquat poisoning and discriminated by support vector machine.

Paraquat is quick-acting and non-selective, killing green plant tissue on contact; it is also toxic to human beings and animals. In this study, we developed a urine metabonomic method by gas chromatography-mass spectrometry to evaluate the effect of acute paraquat poisoning on rats. Pattern recognition analysis, including both partial least squares discriminate analysis and principal component analysis revealed that acute paraquat poisoning induced metabolic perturbations. Compared with the control group, the levels of benzeneacetic acid and hexadecanoic acid of the acute paraquat poisoning group (intragastric administration 36 mg/kg) increased, while the levels of butanedioic acid, pentanedioic acid, altronic acid decreased. Based on these urinary metabolomics data, support vector machine was applied to discriminate the metabolomic change of paraquat groups from the control group, which achieved 100% classification accuracy. In conclusion, metabonomic method combined with support vector machine can be used as a useful diagnostic tool in paraquat-poisoned rats.