AIMTo develop a method for determination of loganin in mouse plasma by using high-performance liquid chromatography. The method was employed to study pharmacokinetics of loganin.

METHODSAn RP-C18 was used as the stationary phase. The mobile phase consisted of methanol-water (30:70), at the flow-rate of 0.8 mL.min-1. The UV absorbance detector was set at 240 nm. Plasma samples were treated with solid phase extraction.

RESULTSThe recovery of loganin in mouse plasma was 86.0%-91.5%. The calibration curve in plasma was linear over the range of 0.01-5.00 micrograms.mL-1. The limit of quantitation was 10 ng.mL-1. The RSDs of intra-day and inter-day (n = 5) were less than 15%. The pharmacokinetic parameters were Cmax = 6.8 micrograms.mL-1, Tmax = 30 min, T1/2 alpha = 26.1 min, T1/2 beta = 29.01 min.

CONCLUSIONThe method is accurate, sensitive and suitable for pharmcokinetic study of loganin. The absorption and elimination of loganin were rapid after ig in mice.

Adjuvants, Immunologic ; blood ; pharmacokinetics ; Animals ; Area Under Curve ; Chromatography, High Pressure Liquid ; methods ; Iridoids ; blood ; pharmacokinetics ; Male ; Mice

OBJECTIVETo study the content variation of triptolide in medicinal material of Tripterygium and provide theoretical basis for the hereditary improvement, the gathering and process, the quality evaluation and the provenance division in medicinal material of Tripterygium.

METHODHPLC method was used to determine the content of triptolide.

RESULTThe relations between triptolide and germplasm, growth year, gathering season were found out basically.

CONCLUSIONThe triptolide contents in xylem are affected by hereditary factors remarkably. While the triptolide contents in phloem are not affected obviously. The accumulation of triptolide needs the certain growth years. However when growth is beyond certain years, the triptolide content decreases with the disintegration of secondary metabolism in xylem. The triptolide in xylem is highest in winter and decreasing in growing season. The triptolide in phloem is less affected by the season.

Chromatography, High Pressure Liquid ; Diterpenes ; analysis ; metabolism ; Ecosystem ; Epoxy Compounds ; analysis ; metabolism ; Phenanthrenes ; analysis ; metabolism ; Plant Roots ; anatomy & histology ; chemistry ; Plants, Medicinal ; anatomy & histology ; chemistry ; growth & development ; Seasons ; Species Specificity ; Time Factors ; Tripterygium ; anatomy & histology ; chemistry ; growth & development ; Xylem ; chemistry

Liquid chromatography/mass spectrometry (LC-MS(n)) has been essential to a large number of quantitative analytical applications in drug research, and especially in the drug PK/PD research, due to its high sensitivity and high specificity. But following the appearance of drugs with high activity and low dosage and the especial structural compounds, a number of limitations of LC-MS(n) have been noted. Derivatization changes the structure of drugs and therefore changes their physical and chemical properties, resulting in high ionization efficiency, low matrix effect and low disturbance by inorganic salts and endogenous compounds in LC-MS(n). In this article, recent progress in the research of the chemical derivatization strategy with LC-MS(n) is reviewed on breakthrough of some LC-MS(n) limitations, in particular focusing on the applications involving some drugs in bio-matrices.
Animals ; Chemistry Techniques, Analytical ; methods ; Chromatography, Liquid ; methods ; Humans ; Mass Spectrometry ; methods ; Pharmaceutical Preparations ; analysis ; Sensitivity and Specificity

This paper developed a sensitive and specific liquid chromatography-electrospray ionization mass spectrometry (HPLC-MS/MS) method for the determination of decapeptide LXT-101 in Beagle dog plasma. Plasma samples spiked with internal standard (IS) were treated with acetonitrile to precipitate the protein. Selected reaction monitoring (SRM) using the precursor --> product ion combinations of m/z 472.1-->587.9 and m/z 502.8-->633.8 were used to quantify LXT-101 and IS, respectively. The linear calibration curves were obtained in the concentration range of 0.5 - 500.0 ng x mL(-1). The limit of quantification (LOQ) was 0.5 ng x mL(-1). The inter-day and intra-day precision (RSD) across three validation run over the entire concentration range was below 10.9%, and the accuracy (RE) was within +/- 1.8%. The main pharmacokinetic parameters of LXT-101 after muscle injection of 20 microg x kg(-1) were as follows, AUC(0-t): (176.8 +/- 116.7) microg x h x L(-1), MRT(0-t): (2.52 +/- 0.53) h, T(1/2): (1.4 +/- 0.3) h; CL: (0.16 +/- 0.09) L x h(-1) x kg(-1), and Vd: (0.30 +/- 0.16) L x kg(-1), respectively. The method is proved to be specific, sensitive and suitable for the investigation of LXT-101 pharmacokinetics in Beagle dog.
Animals ; Antineoplastic Agents ; administration & dosage ; blood ; pharmacokinetics ; Area Under Curve ; Chromatography, High Pressure Liquid ; Dogs ; Gonadotropin-Releasing Hormone ; antagonists & inhibitors ; Injections, Intramuscular ; Male ; Oligopeptides ; administration & dosage ; blood ; pharmacokinetics ; Spectrometry, Mass, Electrospray Ionization

AIMTo test the antiepileptic effect of phencynonate hydrochloride and investigate its antiepileptic mechanism.

METHODSThrough establishment of different epilepsy models, antiepileptic effects of phencynonate hydrochloride and other drugs were examined. Besides, the effect of phencynonate hydrochloride and other compounds against NMDA-induced lethality in mice, NMDA-induced injury in rat primary hippocampal neuronal cultures and NMDA-induced current were also observed.

RESULTSPhencynonate hydrochloride produced a significant anticonvulsant effect on different epilepsy models. Furthermore, phencynonate hydrochloride also exerted its obvious protection against the lethal effects of NMDA in mice, antagonized the NMDA-induced injury in rat primary hippocampal neuronal cultures and blocked NMDA-induced current in a dose-dependent manner.

CONCLUSIONPhencynonate hydrochloride had a notable anticonvulsant effect on typical epilepsy models, its antiepileptic mechanism might relate to its antagonism against NMDA receptor.

Animals ; Animals, Newborn ; Anticonvulsants ; pharmacology ; therapeutic use ; Aza Compounds ; pharmacology ; therapeutic use ; Cells, Cultured ; Electroshock ; Female ; Glycolates ; pharmacology ; therapeutic use ; Hippocampus ; cytology ; Lethal Dose 50 ; Male ; Mice ; N-Methylaspartate ; toxicity ; Neurons ; drug effects ; Neuroprotective Agents ; pharmacology ; Pentylenetetrazole ; Rats ; Rats, Wistar ; Seizures ; chemically induced ; drug therapy

AIMTo study the metabolites of penehyclidine hydrochloride (PH) raceme, a new anticholinerigic drug invented by the Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences.

METHODSThree healthy rat urine samples were collected within 24 h after a single i.m. dose of PH raceme and PH-d5 [(5 + 5) mg.kg-1] simultaneously. The eight metabolites of PH raceme were identified by the methods of LC-MS/MS, GC-MS, FAB-MS and the stable isotope ion cluster. Mass spectrometry was operated in the positive mode for the method of LC-MS/MS.

RESULTSM1 and M1* were identified as the oxygenated products of PH in the cyclopentyl group; M2 and M2* were as the hydroxylated products of PH in the cyclopentyl group; M3 and M3* were as the oxygented and hydroxylated products of PH at the meta-position of cyclopentyl group; M4 and M4* were identified as the dihydroxylated metabolites of PH, the hydroxylated position were at the cyclopentyl group and quiniuclidinol ring of PH. Among them, M1 and M1*, M2 and M2*, M3 and M3*, M4 and M4* were the isomers of each other.

CONCLUSIONThese characteristics can be used for future structure elucidation in studies of the metabolites of PH optical isomers. The structure data of PH metabolites provide important information for the clinical use and for developing better anticholinerigic drug.

Animals ; Cholinesterase Inhibitors ; chemistry ; metabolism ; urine ; Chromatography, High Pressure Liquid ; Male ; Molecular Structure ; Quinuclidines ; chemistry ; metabolism ; urine ; Rats ; Rats, Wistar ; Spectrometry, Mass, Electrospray Ionization ; Stereoisomerism

OBJECTIVEThe study investigates the protective effect on liver of Danxionfang and its components.

METHODMice are injected with CCl4 to establish liver injured model. ALT, AST, serum albumin, globulin in serum and SOD, MDA in liver and liver histological changes were measured to confirm the ability of protecting liver of Danxiongfang.

RESULTThe results show Danxiongfang can inhibit obviously the abnormal increase of ALT, AST in serum and MDA in liver, enhance SOD activity in liver, total protein, albumin, globulin in serum, and decrease liver pathological changes, which suggests Danxiongfang can protect injured liver induced by CCl4.

CONCLUSIONDanxiongfang showed powerful protective effect against liver damage induced by CCl4.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Carbon Tetrachloride ; Chemical and Drug Induced Liver Injury ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Female ; Ligusticum ; chemistry ; Liver ; drug effects ; metabolism ; pathology ; Liver Diseases ; blood ; prevention & control ; Male ; Malondialdehyde ; metabolism ; Mice ; Mice, Inbred ICR ; Phytotherapy ; Plants, Medicinal ; chemistry ; Protective Agents ; isolation & purification ; pharmacology ; Salvia miltiorrhiza ; chemistry ; Superoxide Dismutase ; metabolism

OBJECTIVE: To study the clinical features of children with acute disseminated encephalomyelitis (ADEM) and related recurrence factors. METHODS: A retrospective analysis was performed for the clinical data and prognosis of 73 children with ADEM who were hospitalized from November 2011 to January 2017. RESULTS: Among the 73 children, 41 (56%) had a history of infection before onset and 7 (10%) had a history of vaccination. All children had the symptoms of encephalopathy, including disturbance of consciousness in 47 children (64%) and mental and behavioral disorders in 54 children (74%). Pyrexia was observed in 53 children (73%), dyskinesia in 47 children (64%), headache in 47 children (64%) and vomiting in 40 children (55%). Brain MRI was performed for 65 children and the results showed involvement of the subcortical white matter (83%, 54/65), the deep nuclei (60%, 39/65), the brain stem (58%, 38/65) and the cerebellum (42%, 27/65). Spinal cord involvement was observed in 20 children (20/43, 47%). A total of 15 children experienced recurrence during follow-up. Compared with the non-recurrence group, the recurrence group had significantly higher percentages of children with deep nucleus involvement (P<0.05), with injury in ≥3 spinal segments (P<0.01) and with a time from disease onset to gamma-globulin/hormone treatment of >2 weeks (P<0.05). CONCLUSIONS ADEM in children have various clinical manifestations. A small number of children may experience recurrence. Deep nucleus involvement on MRI, long spinal segmental injury (≥3 segments) and late treatment with gamma-globulin/hormone (>2 weeks) may be associated with the recurrence of ADEM.
Child ; Encephalomyelitis, Acute Disseminated ; Humans ; Magnetic Resonance Imaging ; Prognosis ; Recurrence ; Retrospective Studies

The SARS epidemic is breaking out worldwide. To select suitable herbal drugs for clinical uses is important and urgent amongst the controversial treatment proposals. Nine pharmacological experimental models were used to evaluate the comprehensive efficacy of traditional Chinese remedies by cross validation in different institutes. Eight drugs were optimized for controlling different symptoms of SARS.
Animals ; Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; isolation & purification ; therapeutic use ; Humans ; Multiple Organ Failure ; prevention & control ; Phytotherapy ; Plants, Medicinal ; chemistry ; Severe Acute Respiratory Syndrome ; drug therapy

In order to investigate the central nervous mechanism and the diseases involved in catecholamine transmitter secretion, the dynamics of catecholamine release is studied in single cell, brain slice or in vivo. Noradrenaline is an important neurotransmitter and modulator in the central nervous system (CNS) and the peripheral nervous system (PNS). In the present paper, we first compared three real-time methods used to measure noradrenaline secretion in single cells (membrane capacitance, amperometry and confocal fluorescence microscopy imaging). Compared to the electrophysiological method and fluorescence microscopy, the basic usage of the carbon fiber electrode (CFE) in neuroscience research was presented as an example. Then, we presented a primary description of ion channels, including voltage-gated Na(+), K(+) and Ca(2+) channels in locus coeruleus (LC) neurons in rat brain slices. Finally, we presented example recordings of combined patch-clamp and amperometry measurements in LC neurons, indicating Ca(2+)-dependent quantal noradrenaline release following Ca(2+) influx through Ca(2+) channels.
Animals ; Central Nervous System ; physiology ; Ion Channels ; physiology ; Norepinephrine ; secretion ; Patch-Clamp Techniques ; Rats