Quantification of ambrisentan in human plasma by LC-MS/MS and its pharmacokinetic application / 中国临床药理学与治疗学

AIM: To establish an LC-MS/MS method to determine the concentration of ambrisentan in human plasma and apply it to the study of human pharmacokinetics. METHODS: After extracting ambrisentan and internal standard from human plasma by liquid-liquid extraction, chromatographic separation was performed on a Waters Symmetry C

Single-use Medical Devices Re-processing: Regulatory Status Quo / 中国医疗器械杂志

Some single-use medical devices are reprocessed and reused in some countries in the world, but the regulatory approach is different, and in some countries it isn't regulated yet. In this article, the regulatory status quo of single-use medical devices is reviewed. The regulatory development, important regulatory documents and regulatory approaches of single-use medical device reprocessing in the United States, Germany and the UK are introduced. And how to perform scientific risk assessment and effective risk control is discussed. The information is useful to establish China-specific regulations, and to develop relevant standards, guidelines or specifications and the risk control strategies.

Single-use Medical Devices Re-processing: Risk Assessment and Quality Control Technologies / 中国医疗器械杂志

The reuse of high-cost single-use medical devices (SUD) is permitted in many countries, such as the United States, Germany and the United Kingdom, but strict regulatory requirements must be met. In addition to regulatory policies and regulations, such as market access mode and special requirements on Good Manufacture Practice (GMP), there are strict technical requirements on the potential risk control and quality assurance system. Therefore, effective risk assessment and risk control technology are the keys to ensure effective quality control and safe use of SUDs. In this article, based on analyzing the technological requirements of the national regulatory on SUDs in the United States, Germany and Britain, and combined with the review from latest relevant literature, to discuss the strategies of how to carry out scientific risk assessment. Some risk control technologies on the reuse of SUDs are introduced, which will provide support for the further study on risk control strategies and regulatory decisions for the reuse of SUDs in China.

Optimization, validation and application of an assay for the activity of HMG-CoA reductase in vitro by LC-MS/MS / 药物分析学报

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.

Study on the process of ceramic hydroxyapatite for removing monoclonal antibody aggregates / 中国生化药物杂志

Objective To compare the purification process of two types of ceramic hydroxyapatite(CHT I and CHT II)to remove the aggregates from two monoclonal antibodies(mAb 1 and mAb 2).Methods All the chromatography runs were performed on AKTA AVANT 150 with Tricon 10/50 column.The dynamic binding capacity( DBC) of two types of CHT was studied firstly, and then purification research was carried out selecting the suitable DBC.The column was equilibrated with 5 mmol/L sodium dihydrogen phosphate pH 6.5, and then was eluted with gradient buffers which were 10 mmol/L sodium dihydrogen phosphate pH 6.5 and 2 mol/L sodium chloride pH 6.5.Aggregate content in loading and elution pool was evaluated by size exclusion chromatography.Scale-up process was carried on 20 cm height chromatography column XK16/40.Results DBC of CHT I for mAb 1 was 40 mg/mL and mAb 2 was 45 mg/mL.After purity, monomer content of mAb 1 reached 98.6% and yield was 92.5% and monomer content of mAb 2 reached 98.8%and yield was 91.5%.DBC of CHT II for mAb1 was 16 mg/mL and mAb 2 was 20 mg/mL.After purity, monomer content of mAb 1 reached 99.8% and yield was 91.8% and monomer content of mAb 2 reached 99.9% and yield was 92.2%.Conclusion Two types of CHT both can remove aggregates effectively from monoclonal antibodies when aggregate content reaches more than 10%, and results conform to the regulations.CHT I has higher dynamic binding capacity than CHT II, and CHT II is superior to CHT I in removing aggregate efficiency.The purification process is simple and can be easily scaled up in pilot and manufacture.Therefore, it meets the requirement pilot and scale production.

Pharmacokinetics and pharmacodynamics of sustained-release implant of goserelin in rats / 中国药理学与毒理学杂志

OBJECTIVE Toillustratethepharmacokineticsandpharmacodynamicsofdifferentdos-agesofsustained-releaseimplantofgoserelininrats.METHODS Theratsreceivedasingledoseof sustaineed-release i mplant of goserelin 0.3,0.6 and 1 .2 mg per rat by subcutaneous injection,respec-tively.Concentrations of goserelin and testosterone in plas ma were determined by HPLC-MS/MS.The pharmacokineticparameterswerecalculatedbyWinNonlin6.3.RESULTS Themainpharmacokinetic parameters of the 0.3,0.6 and 1 .2 mg per rat were as fowllows:the area under the concentration-time curve(AUC0-t)was 770 ±96,1534 ±299 and (3233 ±777)μg·L-1·h,and the maximum plasma con-centration(cmax)was 3.7 ±0.3,6.8 ±2.2 and (1 7.6 ±5.4)μg·L-1 ,respectively.Regression analysis was applied to analyze the relationship between AUC0-t and cmax at different doses and those relative coefficients were 0.942 and 0.923 respectively.AUC0-t and cmax increased with the dose in the range of 0.3-1 .2 mg per rat.As for other main pharmacokinetic parameters (peak time,half life,mean resi-dence time,clearance and apparent volume of distribution),there was no significant difference between the three groups.Testosterone plasma concentration reached the highest level following administration and then kept decreasing to low concentrations.Between 28 d and 35 d,testosterone plas ma concentra-tionslowlyincreasedtothenormallevel.CONCLUSION Pharmacokineticcharacteristicsofsustained-release implant of goserelin in rats show a linear relationship,within the dose range of 0.3-1 .2 mg per rat.The results from pharmacodynamic data show that testosterone does not change in a dose-depend-ent manner at a dose ranging from 0.3 to 1 .2 mg per rat.Testosterone plasma concentration decreases to theoretical castrate level (0.5 μg·L-1 )after 4 d following a dose of 0.6-1 .2 mg per rat.

Preparation and in vitro and in vivo evaluation of HupA PLGA Microsphere

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

Isoflavones from vines of Pueraria lobata / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the isoflavones from the vines of Pueraria lobata.</p><p><b>METHOD</b>The compounds were isolated by column chromatography over silica gel and RP-C18, and purified by Sephadex LH-20 column chromatography and preparative TLC. The structures were elucidated on the basis of physico-chemical properties and spectral data.</p><p><b>RESULT</b>Twelve compounds were isolated and identified as: 3'-methoxydaidzein (1), formononetin (2), genistein (3), daidzein (4), daidzin (5), genistin (6), ononin (7), 5-hydroxyl ononin (8), calycosin (9), 6"-O-acetyl genistein (10), 6"-O-acetyl daidzin (11), puerarin (12).</p><p><b>CONCLUSION</b>For the first time, compounds 9-11 were isolated from the genus Pueraria plant, and compounds 1, 3, 6-8 were obtained from the vines of this plant.</p>