Objective To develop a sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for the determination of forsklin in rat plasma.Methods After extraction with methyl tert-butyl ether,chromatographic separation was performed on a C18 column with the mobile phase consisting of water ( 0.1％ formic acid)-acetonitrile in a gradient elution mode.A tandem mass spectrometer equipped with electrospray ionization (ESI) source was used as detector in the positive ion mode.Quantification was performed using multiple reaction monitoring (MRM) with the precursor product combination ions of m/z 411→375.3 and 285→193 for forsklin and diazepam.Results Good linearity was obtained in the 0.5-1000 ng/ml range for the analyte and the analytical method was validated in terms of specificity,precision,accuracy,recovery,stability and matrix effect.These assays gave RSD values always lower than 14.4％ and RE values between -3.5 ％ and 3.8％.In addition,the specificity,extraction recovery,stability and matrix effect were satisfactory.Conclusion Due to its high sensitivity,specificity and simplicity,the method could be used for pharmacokinetic studies of forsklin.

Objective To develop a HPLC-MS/MS method for the determination of aconitine and study thein vitro metabolic stability of aconitine in dog tissue homogenates.Methods The chromatographic separation was performed on a C18 column.The mobile phase consisted of acetonitrile and water with 0.2％ formic acid and 5 mmol/L ammonium acetate.A triple quadrupole tandem mass spectrometer equipped with an electrospray ionization interface source was used for the quantitative determination in the positive selective reaction monitor mode.Aconitine was incubated with dog tissue homogenates and samples were withdrawn at different time points and precipitated by acetonitrile with internal standards citalopram.Results Aconitine showed good linear relationship over the range from 5 to 500 ng/ml.The recoveries of aconitine were between 85.73％ and 92.12％ at three QC concentration levels.The intra- and inter-day precisions were 5.32％ - 8.95％ and 5.45％ - 8.86％,respectively.After incubation,about 20％ of aconitine were cleared in the liver and small intestine,and t1/2 were 460.6 and 521.3 min,respectively.But none was metabolized in the stomach and kidney.Conclusion These results demonstrated that aconitine was mainly metabolized in the liver and small intestine at a slow rate.

Objective To establish a HPLC method for the determination of quercetin from different parts of L. cuncata(Dum. Cours.)G.Don.,including roots,old branches,young shoots,leaves and seeds,and to build the fingerprints. Methods The HPLC method determination of quercetin and fingerpints were establised. Results The restults showed that there were great differences be?tween the quercetin contents from different parts,with the highest contents found in seeds,followed by young shoots,leaves,old branches,and roots. The similarities of HPLC fingerprints of the medicinal material were quite different from the parts of L. cuncata (Dum.Cours.)G.Don.. The similarities were all above 0.95 for L. cuncata(Dum.Cours.)G.Don. samples,roots,old branches and young shoots below 0.85,leaves and seeds similarities below 0.60. Conclusion It was concluded that different parts(such as roots, old branches,young shoots,leaves,seeds)of L. cuncata(Dum.Cours.)G.Don. should be divided in clinical and productive practice so as to supply the scientific basis for enhancing the curative effect and reasonable utilization of the resource of L. cuncata(Dum.Cours.)G. Don.

In the second half of 2016,the U.S. Food and Drug Administration(FDA)approved 7 new molecular entities and 3 new Biologic License Application(BLA), the lowest number in recent years. According to the prescription information for profes-sionals,this article introduced the description,mechanism of action and clinical studies and briefly describes the boxed warning,indi-cations and usage,dosage and administration,dosage form and strength,contraindications,warning and precautions,adverse reac-tions,drug interaction and the use in the special population. In addition,the first and critical events in the history of new drug develop-ment and reaserch were emphasized.

Anthrax is a malignant infectious disease caused by Bacillus anthracis spores,after entering the host Bacillus an-thracis produces and releases anthrax toxin,which is the main cause leading to death of the host. The anthrax toxin is composed of two enzymatically active components:lethal factor(LF)and edema factor(EF),and one shared receptor binding and translocation com-ponent:protective antigen(PA). PA combined with LF is called lethal toxin(LeTx),while PA combined with EF called edema toxin (EdTx). Currently,the main drugs for treating anthrax are antibiotics,but antibiotics can only kill part of anthrax spores and bacte-ria,and cannot inhibit the activity of anthrax toxin. So it is necessary to develop novel drugs for inhibiting anthrax toxin. This review summarizes the evolution of small-molecule inhibitors of anthrax toxin respectively targeting PA,LF and EF.

Under physiological conditions, many vital functions of the body are controlled by transient release of bioactive substances at a specific time and site. Based on the circadian rhythm character of disease and chronotherapeutic conceptions, pulsatile delivery system has been designed to achieve optimal therapeutic effect and reduce the toxic and side-effect. In recent years, more and more studies are focused on the pulsatile multiparticulate drug delivery system. Pulsatile multiparticulate system possesses many benefits, such as no risk of dose dumping, predictable gastric emptying, flexible release patterns and increased bioavailability. Based on these premises, the aim of this review is to summarize the major design methods of pulsatile multiparticulate and the research progress.

The chemic al composition of traditional Chinese medicine (TCM) is the material base for its prevention and treatment of disease. Characterization, analysis and isolation of chemical constituents, important fields of modern research on TCM, however, are still a great challenge due to the complexity. In recent years, considerable progress has been made in these fields with the application of new chromatographic packing materials and methods, analysis technologies represented by LC-MS and the associated databases and softwares. Here, the advancement of methods and strategies used in the research on the chemical constituents of TCM is briefly reviewed.

Parkinson′s disease(PD),the second neurodegenerative disease in the world,is characterized by a combination of motor symptoms(rest tremor,bradykinesia,rigidity,postural instability,stooped posture and freezing of gait)and non-motor symp?toms(including psychiatric and cognitive disorders). The core neuropathological features of PD are the loss of dopaminergic neurons in the substantia nigra and the deposition of iron and cytoplasmic protein aggregates(Lewy bodies)inside neurons. Currently,clinical treatment for PD is symptomatic and there is no effective treatment to restore neuronal degeneration. In the PD therapy ,medication re?mains dominant. Anti-PD drugs are mainly based on the critical signal pathways or some specific targets which play a key role in the pathogenesis of PD to relieve the symptoms of PD. Research and development in novel drugs to prevent or treat PD have been a crucial subject,and some novel candidates are under development. In this paper,we summarize and analyze the anti-PD drugs,and make a brief discussion about its pharmacological targets.

Luteinizing hormone(LH)is a gonadotropin of hypothalamic-pituitary-gonadal axis(HPG),secreted by the anteri?or pituitary. The secretion of LH is directly controlled by the release of gonadotropin releasing hormone(GnRH),acts at the ovaries and testes to stimulate the production of gonadal hormones. Aging leads to increases in LH,and higher serum levels of LH has been ob?served in Alzheimer′s disease(AD)patients when compared to age-matched controls. Evidences from basic research and epidemiologi?cal investigation support the critical role of elevated LH in pathogenic process of AD and deteriorating cognitive decline. Here we sum?marize the recent discoveries containing human AD epidemiological evidence for LH,cognitive impairments resulting from LH activi?ty,LH in AD pathology and LH receptor signaling mechanisms.

Alzheimer′s disease(AD)is one of the most common causes of cognitive impairment.“Aβhypothesis”and“tau protein aggregation hypothesis”are two representative hypotheses in relation to AD pathology. But recently,therapeutic strategy target?ing on reducing Aβdeposition failed in clinical trials. On the other hand,as the phosphorylation of tau protein is regulated by multiple upstream kinases,inhibition of a single kinase usually cannot effectively suppress the aggregation of the tau. While blocking multiple kinases at the same time will produce serious side effects. Currently,targeting on Aβand tau protein get into awkward situations. In view of this,researchers are looking for new drug targets for improving cognitive function. Phosphodiesterase 4(PDE4 4)is an enzyme responsible for the hydrolysis of cAMP in the body. There are four subtypes for PDE4,and PDE4A,B and D are highly expressed in the central nervous system. Inhibition of PDE4 causes activation of cAMP/PKA/CREB/BDNF signal pathway,which is beneficial for the strengthening and consolidation of learning and memory. This review will focus on the most recent evidence regarding the role of PDE4 in learning and memory.