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A stable HMG-CoA reductase (HMGR) reaction in vitro was developed by a sensitive, selective and precise liquid chromatography–tandem mass spectrometry (LC–MS/MS) method. The optimized enzyme reac-tion condition contained 1.5μg of HMGR, 20 nM of NADPH with 50 min of reaction time. The method was validated by several intra-and inter-day assays. The production transitions of m/z 147.0/59.1 and m/z 154.0/59.1 were used to detect and quantify mevalonolactone (MVAL) and MVAL-D7, respectively. The accuracy and precision of the method were evaluated over the concentration range of 0.005–1.000μg/mL for MVAL and 0.010–0.500μg/mL for lovastatin acid in three validation batch runs. The lower limit of quantitation was found to be 0.005μg/mL for MVAL and 0.010μg/mL for lovastatin acid. Intra-day and inter-day precision ranged from 0.95%to 2.39%and 2.26%to 3.38%for MVAL, 1.46%to 3.89%and 0.57% to 5.10% for lovastatin acid, respectively. The results showed that the active ingredients in Xuezhikang capsules were 12.2 and 14.5 mg/g, respectively. This assay method could be successfully applied to the quality control study of Xuezhikang capsule for the first time.
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Acetylcholinesterase inhibitors [AChEIs], including Huperzine A [HupA], have been the mainstay of treatment for Alzheimer's disease [AD]. However, AChEIs can cause gastrointestinal side effects, which has been related to the high C[max] and short t[max] after oral administration. Clinical trials have verified that extended-release formulation with lower C[max] and prolonged t[max], such as rivastigmine patch, could perform a similar efficacy with significantly improved tolerability compared with the oral formulations. In this study, we developed an extended-release microspheres formulation of HupA [called as HAM] with poly[lactide-co-glycolide] [PLGA] as drug carrier. HAM has showed the loading rate as 1.35% [w/w] and yielded 42% with mean particle size at 72.6 micro m. In vitro and in vivo pharmacokinetics studies have showed that HAM produced a relatively smooth and continuous drug concentration in 14 days. Furthermore, in vivo pharmacokinetics data have demonstrated that the C[max] was lower and the t[max] was considerably later in single intramuscular administration of HAM [1,000 micro g/kg] than the counterparts in single intragastric administration of HAT [75 micro g/kg/d]. Meanwhile, HAM has performed a continuous inhibition to brain AChE activity in normal rats and improvement of memory deficit in A beta 1-40 i.c.v. infused AD rat model for 14 days. The results have suggested that HAM has performed good extended-release properties and good prolonged pharmacological efficacy in vivo in the 2-week period, and could exert a similar efficacy with significantly lowered gastrointestinal side effects as compared with oral formulation
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OBJECTIVE To investigate the risk factors for vancomycin-resistant Enterococcus(VRE) infections and their effective isolation measures.METHODS The data of 21 cases of VRE nosocomial infections were analyzed from Jul 2003 to Dec 2005 in Beijing Chaoyang Hospital;28 cases of antibiotic-sensitive Enterococcus infection were randomized as control.T test,chi-square test and Logistic regression analysis were used for statistics.Strict measures were taken to all of the VRE infected patients.RESULTS According to univariate analysis,the factors associated with the development of VRE nosocomial infection were age,in ICU,accepted invasive operation,Acute Physiology and Chronic Health Evaluation Ⅱ(APACHEⅡ),live in hospital more than 30 days,co-infection with other pathogens,and fluoroquinolone and vancomycin/norvancomycin use 15 days before isolation of VRE.Multivariate Logistic regression analysis identified two independent factors: accepted invasive operation and previous vancomycin/norvancomycin use.Spreading of VRE had not occurred.CONCLUSIONS Accepted invasive operation and previous vancomycin/norvancomycin use are independent risk factors for VRE infection.Effective measures can prevent the spread of VRE.
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OBJECTIVE To search for the sensitive factors of infection by vancomycin-resistant Enterococcus(VRE) as well as the corresponding prevention measures. METHODS Investigation and analysis had been conducted for 15 cases of infection induced by VRE. RESULTS Some of the cases had been infected in communities,but most been infected in hospital,including the old patients in ICU,patients with underlying diseases or respiratory diseases and inpatients staying long in hospital.The infection site was mainly lower respiratory tract,together with the positive results of drug-resistant staphylococci culture. CONCLUSIONS Use of large amount of strong effect broad-spectrum antibiotic as well as use of invasive mechanical ventilation are the risk factors causing infection by VRE.Alternative use of antibiotic of ?-lactamases,amino-glycosides and quinolones can cure the infection,besides,strict isolation and disinfection measures can prevent the infection from spreading in hospital.