The U.S. Food and Drug Administration(FDA) approved 53 new drugs into the market in 2020, including 38 chemical small molecules and 15 biological products. According to the prescription information for professionals and the related literature as well as patent information, this review describes the descriptions, indications, mechanism of action, dosage form and strength, adverse reactions, and one synthetic route of the chemical small molecules, and brief information about the biological products.

Semaglutide was synthesized by solid-liquid phase synthesis. Both the linear peptide Aib8, Arg34GLP-1(7-37) and aliphatic side-chain acylating agent were obtained using solid-phase synthesis, and the Lys26 amino acid was subsequently modified by using the latter one in alkaline condition. A homogeneous time-solved fluorescence resonance energy transfer (TR-FRET) was performed to evaluate the bioactivities of the self-synthetic samples. The results showed that the bioactivities of the two samples from different batches were identical, and its EC50 was half of Liraglutide's. In conclusion, this process technology has several advantages such as cheap material and high yield in the industrial production.

As packaging and delivery system combined products, pre-filled syringes (PFS) are becoming increasingly popular in the field of biopharmaceutical products for their own advantages. However, the development of biopharmaceutical products in PFS presents its own distinctive challenges. The components of the PFS are likely to interact with the drug, in particular, issues involving incompatibility with silicone oil which often be used as a lubricant. Silicone oil will migrate into injection to form droplets, which may induce aggregation of protein, resulting the formation of insoluble particles and other issues. Therefore, this paper reviews the development of PFSs, the siliconization technology for PFSs, the insoluble particles caused by silicone oil and the solutions to this matter.

随着中国GMP2010 版的实施，风险管理已广泛运用于制药行业，而变更控制作为制药质量体系要素之一，如何将质量风险管理有效运用到变更控制中，是众多企业面临的主要问题。本文根据质量风险管理的理念和工具，将变更控制的评估分为初步的风险评估和详细的风险评估，同时介绍了基于风险管理的变更控制方法以及如何将质量风险管理集成到现有的变更控制系统，使变更控制评估更加充分、有效，从而确保变更带来的风险得到有效的控制，保证产品质量和患者安全。

Dry powder inhalers (DPIs) have been one of the research hot spots in recent years, with an excellent application prospect. Research and development of DPIs have strict requirements on powder characteristics of dry powder. Properties of active pharmaceutical ingredients, carriers and additives, environment and processing conditions decide the relative strength of the inter-particle forces, then affect the macroscopic properties of the powder. Understanding the powder properties by a variety of means, selecting the optimal processing conditions and formulation patterns, device design are the keys to the research and development of DPI formulation. Recently, DPIs prepared by novel engineering technology such as TechnoSphere? and PulmoSpheresTM have been on market.

本文阐述了仿制药研发中如何根据原研制剂杂质谱剖析测得结果，来科学合理地制订仿制原料药与仿制制剂中杂质控制策略，并从临床用药的宏观角度和具体杂质研究的微观思路上阐明杂质研究中应把握的“度”，为仿制药杂质的理性研究提供一些借鉴。

The U.S. Food and Drug Administration(FDA) approved 48 new drugs into the market in 2019, including 38 chemical small molecules and 10 biological products. According to the prescription information for professionals and the related literature as well as patent information, this review describes the descriptions, indications, mechanism of action, dosage form and strength, adverse reactions, and one synthetic route of the chemical small molecules, and brief information about biological products.

Gefitinib (1) is a novel medicament for a targeted tumor therapy. It is used in the treatment for latestage non-small cell lung cancer. The marketed formulation of 1 is tablets with low absorption and oral bioavailability. However, the adverse reactions of 1 are exacerbated with the increasing of dosage. To improve the poor oral bioavailability of 1, its inclusion complexes had been environmental-friendly synthesized by mechanochemical technology with GMS 10-8 roll mill in this study. Arabinogalactan (AG) and hydroxypropyl-β-cyclodextrin (HP-β-CD) were separately used as inclusion carriers for 1. The synthesized complexes were characterized by nuclear magnetic resonance (NMR) relaxation technique (T2), scanning electron microscopy (SEM), differential scanning calorimetry(DSC), powder X-ray diffraction (P-XRD). Results of in vitro tests showed that the solubility of 1 was increased from 0.77 g/L to 2.16 g/L, and the dissolution at 120 min was increased from 60％ to 92％ of its mechanochemical treated complexes with HP-β-CD. Similarily, the solubility of 1 in its complex with AG was increased to 1.32 g/L, and the dissolution at 120 min was increased to 75％. Pharmacokinetic behaviors of these inclusion complexes were investigated with male SD rats as the animal models. The rats were divided into 4 groups: injection group with 1 (10 mg/kg), intragastric administration groups with 1, 1/AG inclusion complexes or 1/HP-β-CD inclusion complexes (50 mg/kg). Results showed that the absolute bioavailability of 1 in rats with intragastric administration were 56.94％, 81.63％ and 78.48％ for 1, 1/AG inclusion complexes and 1/HP-β-CD inclusion complexes, respectively. In conclusion, the two synthesized complexes of 1 were in formation of the inclusion, with increased solubility, dissolution in vitro and absorption in vivo. It indicated that the mechanochemical technology was a promising approach to develop 1 solid oral dosage forms with decreased dosage and improved oral bioavailability.

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The pharmaceutical films are single- or multi-layer sheets with a size of postage stamp, which can be referred as a drug release platform used for both local and system action via oral, buccal, sublingual, ocular, vaginal and dental routes. The study of films in China can be traced back to 1970s, while the contraceptive films for vaginal administration were developed by China State Institute of Pharmaceutical Industry. And the current Chinese Pharmacopoeia on this dosage form was updated on the 1985 edition. Compared with the traditional dosage forms, the pharmaceutical film can be considered as a versatile drug delivery system with several clinical advantages, including convenient administration, high patient compliance and enhanced bioavailability. Furthermore, a prolonged drug release and lowered administration frequency can be achieved by using suitable polymers. This paper focuses on the research and application progress of pharmaceutical films, and aims to provide an overview of their formulation, production progress, particular features, and quality evaluation methods.

Ibuprofen is one of the most widely used NSAIDs in clinical, and it has a history of over 50 years for use. In order to obtain more active compounds or to reduce ibuprofen’s adverse reactions, structural modifications of ibuprofen have been developed in recent years. In this review, various studies in structural modifications of ibuprofen are summarized according to different strategies, and some recent organic synthetic methodologies are also introduced to provide a reference for the development of modification.

The synthetic process of the antiviral drug rilpivirine hydrochloride(1) was improved. Ethyl formyl acetate(2) reacted with S-methylisothioure(3) to give 2-(methylthio)-4-hydroxyl-pyrimidine(4). Compound 4 reacted with 4-aminobenzonitrile(5) in ethylene glycol dimethyl ether in the presence of methanesulfonic acid to give 4-[(4-hydroxypyrimidin-2-yl)amino]benzonitrile(6), and the reaction temperature decreased from 200 ℃ to 110 - 120 ℃. Compound 6 reacted with HBr/CH3COOH to obtain 4-[(4-bromopyrimidin-2-yl)amino]benzonitrile(7). 4-Bromo-2,6-dimethylaniline(8) reacted with acrylonitrile(9) in the presence of palladium acetate and tris(Omethylphenyl) phosphine instead of 10％ Pd/C to give (E)-3-(4-amino-3,5-dimethylphenyl)acrylonitrile(10), by which the cis-isomer was reduced from 20％ to 0.60％. Meanwhile, compound 10 was purified by recrystallization instead of column chromatography in the work-up, so that the yield of this step was increased from 48％ to 87％. Compound 7 was condensed with 10 under the action of 1,1,3,3-tetramethylguanidine(TMG) as acid binding agent, and the title compound in a purity of 99.92％ was obtained via a salt formation with oxalic acid, and the content of cis-isomer was reduced to 0.08％. The improved process was simple and convenient with a total yield of 52％(based on 2).

A pharmaceutical cocrystal is a crystalline material comprising an active pharmaceutical ingredient (API) and a cocrystal coformer (CCF). API and CCF have definite stoichiometric amounts in pharmaceutical cocrystal molecules. Preparation of pharmaceutical cocrystals is an efficient method to improve the physicochemical properties of poorly soluble drugs. Study on dissolution behavior is one of the hot spots in the field of pharmaceutical cocrystal. This paper summarizes the research progress in pharmaceutical cocrystal screening, preparation and dissolution process, and puts emphasis on discussing the research methods and results about dissolution of pharmaceutical cocrystals. The measurement methods of equilibrium solubility (or apparent solubility) and intrinsic dissolution rate are described. UV imaging dissolution system is introduced, which can carry out in situ monitoring of cocrystal dissolution and provide real time UV image about dissolution process. For theoretical studies on dissolution, two functions have been put forward by Rodríguez-Hornedo's research group to calculate intrinsic solubility of pharmaceutical cocrystal and solubility at eutectic point. Solubility obtained theoretically by calculation can provide essential information for cocrystal screening, preparation and formulation. During cocrystal dissolution process, high solubility of pharmaceutical cocrystal results in a supersaturation of poorly soluble APIs and further crystallization of APIs, which is called solution mediated phase transition (SMPT). The advantage of pharmaceutical cocrystal on improving API dissolution rate can be lost if the SMPT phenomenon happens. Research progress on inhibition of SMPT has also been introduced in this paper.

This article summarizes the patents, mechanisms, indications, dosage forms, specifications and synthetic routes of 22 chemical drugs currently used in clinical trials for the treatment of COVID-19 in China, which is expected to provide a useful reference for research institutions and pharmaceutical companies engaged in anti-SARSCoV- 2 drug research.

Polymorphism is a prevalent phenomenon for drugs. Polymorphs of one drug are chemically identical, however, their physical and chemical properties are different. Therefore, polymorphism is an important part of research content for drugs. In terms of drug quality control, bioavailability of various polymorphs may be different. Polymorphism is an important factor for the clinic effect of drugs, and has strong influence on the stability of drug crystallization and the post processing (filtration, drying, preparation, et al). Progresses on the screening and control of polymorphism, process analysis of crystallization, and engineering were summarized and analyzed in this article. Perspectives of development of continuous crystallization and the numerical simulation for industrial crystallization in the future were also given.

Pacritinib hydrochloride was synthesized from 2-hydroxy-5-nitrobenzaldehyde by nucleophilic substitution with 1-(2-chloroethyl)pyrrolidine hydrochloride to give 5-nitro-2-[2-(pyrrolidin-1-yl)ethoxy]benzaldehyde, then followed by reduction, substitution, reduction and salification to obtain 3-[(allyloxy)methyl]-4-[2-(pyrrolidin-1- yl)ethoxy]aniline ditoluenesulfonate, which was subjected to condensation with 4-[3-[(allyloxy)methyl]phenyl]-2- chloropyrimidine, and olefin metathesis with an overall yield of about 13％(based on 2-hydroxy-5-nitrobenzaldehyde).

The U.S. Food and Drug Administration (FDA) approved 46 new drugs into the market in 2017,including 34 chemical small molecules and 12 biological products. According to the prescription information for professionals and the related literature as well as patent information, this review describes the descriptions, indications,mechanism of action, dosage form and strength, adverse reactions, and one synthetic route of the chemical small molecules, and brief information about biological products.

In this review, the necessary background and some concepts related to genotoxic impurities are introduced. The alert structure of potential genotoxic impurities commonly found in drug synthesis are given, and the process were analyzed and classified by case studies. The use of ACP(avoid-control-purge) strategies and methods are shown for controlling and purging GTI, and some successful cases and progress from multinational pharmaceuticals are analyzed.

The U.S. Food and Drug Administration (FDA) approved 45 new drugs into the market in 2015, including 32 chemical small molecules and 13 biological products. According to the prescription information for professionals and the related literature as well as patent information, this review describes the  descriptions, indications, mechanism of action, dosage form and strength, adverse reactions, and one synthetic route of the chemical small molecules, and brief information about biological products.

印度仿制药产业无论在医药制度、创新意识及国际化战略等方面都先于我国，已建立了全球竞争优势。本文比较中印两国仿制药产业在获批情况、医药制度、质量认证及国际化模式等方面的差异，为我国仿制药提高国际竞争力提出建议。我国应把握国家医药国际化战略机遇，借鉴印度成功经验，确定适合我国医药国际化发展的道路。

药学研究阶段是药品研究的基础部分，在此阶段建立质量管理体系对研究过程进行管控，有利于后续研究及药品最终质量的保证。本文介绍了天津市汉康医药生物技术有限公司药学研究部门的质量管理体系建立的过程及执行后的效果分析。对实际建立过程总结经验并提出建议，以期为药学研究过程的质量管理提供实例参考。

On the basis of a literature survey, this paper summarizes the characteristics and applications to oral solid preparations of Eudragit, a series of commonly used pharmaceutical excipients. The film forming process of Eudragit depends on its minimum film forming temperature (MFT) and glass transition temperature (Tg). Eudragit polymers can be divided into pH- and osmotic-dependent acrylic resins. pH-Dependent acrylic resins can be dissolved in different
pH media and with popular applications to the site-specific delivery systems. For example, the Eudragit series E are commonly used in solubilization, taste-masking, moisture-protection. Osmotic-dependent resins can be used as sustainedrelease materials. Moreover, several application technologies, such as EudrapulseTM, EudramodeTM and EudracolTM, based on the combination of insoluble Eudragit and other materials, are developed to regulate the drug release rate. In addition, the applications of Eudragit to novel pharmaceutical technologies (3D printing and electrostatic spinning) are briefly introduced.

Isolation technology has been widely implemented in the pharmaceutical industry, which is developing rapidly in recent years. Vaporized hydrogen peroxide (VHP) sterilization has become a common option in isolation technology. However, some VHP-sensitive peptides and items (such as stoppers, primary packaging materials, etc) were not suitable for VHP sterilization due to the strong oxidizing property. It was confirmed that VHP could penetrate breathe bags and bioprocess containers. So, the resistance performances of packaging containers with different compositions were investigated by determining VHP concentration changes in bags during the sterilization process. The results showed that four packing containers of ultralow density polyethylene (ULDPE)/ethylene-vinyl acetate copolymer (EVA)/ethylene vinyl alcohol (EVOH)/ULDPE, polyethylene (PE)/EVOH/ULDPE, polyester/EVOH/PE and polyamide/EVOH/PE/PE/ ULDPE could prevent VHP penetration.

本文以日本创新药物的审批管理政策为研究对象，分析目前日本创新药物审批管理现状，并结合量化数据探讨政策实施效果。结果显示，日本创新药物审批管理在提升新药的上市速度、上市数量及临床价值方面均产生了显著效果，激发了制药企业的创新热情，保障了公众用药需求，并引导了产业对于药品社会效益的关注。建议我国从构建多种特殊审评通道，明确专家审议的法律地位及完善沟通咨询体系的建设三方面，对创新药物审批管理政策进行调整和完善。

2016 年作为“十三五”开局之年，我国医药工业主要经济指标表现较好，均呈现稳步回升态势，主营业务收入增速一直保持在10％以上，较上年同期明显回升；利润总额表现突出，增速已超过15％，处于近两年来的最高水平。2016年底医药制造业工业增加值增速为10.8％，不仅较上年同期上升0.9 个百分点，且高出全国工业增加值4.8 个百分点，在全国工业各行业中排名靠前。

基于对注射剂风险控制认识的不断加深，我国药监部门大幅提高了注射剂的研发及评价的技术要求。近年，注射剂的变更申请数量较大。本文在梳理日常技术审评工作的基础上，结合近年未获得批准的部分注射剂变更申请的案例分析，对注射剂变更研究的思路、现状和存在的问题进行了分析。

虽然药品上市许可持有人(Marketing Authorization Holder，MAH) 制度自2016 年已经开始试点，但是MAH 制度与现行制度尚不能有效衔接，如果不及时完善这些问题，将导致在实施过程中存在诸多盲点与漏洞，不利于MAH 制度的推广。本文梳理了MAH 制度在实施过程中与现行制度的矛盾点，并提出自己的思考与建议。在借鉴国外经验的基础上结合我国实际情况，提出合理的解决措施，通过理顺这些问题使我国MAH 制度顺利施行。

The residual water in raw materials and reaction system is not conducive to the synthesis of chemical drugs, and water content in bulk drugs and pharmaceutical preparations affects the stability, physical and chemical properties, dissolution and pharmacological effects. Therefore, residual water is almost a must-test item in the synthesis, and it is important to strictly control the water content in the reaction system by effective water removal methods. To provide some references for water removal in drug synthesis, this paper reviews the existence forms of water, common dewatering agents and dehydrating agents as well as their action principles and abilities of removing water. The applications of water removal in the synthesis of chemical drugs are briefly introduced.

日本自1950 年实施药价基准制度起，就建立了医保药品支付价格调整机制，在管控药品价格、降低药品和医疗费用支出、保证价格公开合理等方面取得了显著成效。本文首先系统分析了日本支付价格调整制度，包括调整原则、调整依据、调整方法和价格公示四个方面，然后实证分析了日本支付价格调整制度的实施效果。最后借鉴日本支付价格调整经验，提出构建我国医保药品支付标准调整机制的意见和建议。

A rapid, sensitive and selective UPLC-MS/MS method was developed for the simultaneous determination of enalapril and enalaprilat in human plasma. Chromatographic separation was achieved on a Waters Acquity UPLC BEH column, with the mobile phase of 80％ methanol (containing 0.5％ formic acid, A) and 0.5％ formic acid (B) at a flow rate of 0.3 ml/min. A tandem mass spectrometric detection with an electrospray ionization (ESI) interface was conducted via multiple reaction monitoring (MRM) under positive ionization mode. Linear calibrations were achieved in ranges of 0.5-200 ng/ml for enalapril and 0.2-80 ng/ml for enalaprilat in human plasma. The intra- and inter-day precisions were below 2.9％ for enalapril and below 9.4％ for enalaprilat, and the deviations of accuracies were -2.86％-1.04％. The average recoveries of enalapril and enalaprilat were 99.71％ and 99.59％, respectively. There was no significant matrix effect, hemolyzed effect or hyperlipidemic effect for enalapril and enalaprilat. This method was successfully applied to a fasting and fed pharmacokinetic study of enalapril maleate in Chinese volunteers.

N-Cyclopropyl-1H-imidazole-1-carboxamide (4) was prepared by the reaction of cyclopropylamine with N,N'-carbonyldiimidazole instead of the highly toxic phenyl chloroformate. Then compound 4 was subjected to a substitution with 4-(4-amino-3-chlorophenoxy)-7-methoxyquinoline-6-formamide to afford lenvatinib with a total yield of 73％, and a purity of 99.2％. This process has some advantages such as high yield, simple operation, and it is suitable for industrial production.

In recent years, there have been great advances in the development of drug delivery system based on nanoparticles, while they are found to be immunogenic and nanotoxic. Therefore, as a safer and more efficient vector, cell membrane has become a hot research area. Incorporating cell membranes onto nanoparticles enables the nanoparticles having better biocompatibility. Moreover, through modifying with different types of cell membranes, such as blood cells, stem cells and bacteria cells, the nanoparticles will get valuable characters, such as better targeting, lower chance to be recognized by immune system and longer systemic circulation time. In this review, the fabrication processes, characters and applications of cell membrane-camouflaged nanoparticles are introduced to promote the application of nanoparticles
to drug delivery system.

The aim of the present work was to develop a benzoyl peroxide (BPO)(5％) gel for skin acne vulgaris treatment, and the evaluation of in vitro equivalance to the reference listed drug (RLD), Benzihex? AC, was carried out. The formulations of the gel were formulated by employing Carbopol 980 as hydrophilic matrix and poloxamer 407 as sorbefacient. Optimization of formulation was supported by agar diffusion method and the following factors were investigated through single factor screening at three levels: the partical size of BPO (100-400 mesh number), the concentration of Carbopol 980 (1.0％-2.0％) and poloxamer 407 (0.1％-0.3％). The response variables was the diffusion distance in agar. The optimized gel had similar in vitro release profiles to the RLD based on the similarity factor (f2). The delivery amounts of BPO into and through the pig skin from the optimized gel were compared to those from RLD. Both gels showed consistent behavior: the stratum corneum uptake and skin penetration of BPO from the two gels were generally comparable. Taken together, the results of this research provided a generic BPO gel that was in vitro equivalent to the RLD.

Cubosomes are bicontinuous cubic phase liquid crystals, consisting of two non-intersecting water channels and highly twisted bicontinuous lipid bilayer in three dimensions. As a lipid carrier system, cubosomes are attracting more and more attention due to the unique liquid crystalline structures and physicochemical properties. Recently, outstanding properties of cubosomes such as high stability, biodegradability and bioadhesion make them excellent candidates for drug-delivery applications and provide the ability to incorporate and deliver drug molecules in a controlled manner. Through retrieving the related literatures from PubMed, CNKI, CQVIP and WANFANG databases with “cubosomes”, “cubic liquid crystalline” and “cubic phase nanoparticles” as keywords, this paper mainly reviews the formation mechanism of cubosomes, the influencing factors for the phase transition of cubosomes and the application to delivery of natural drugs, so as to provide references for the design and development of cubosomes.

本文通过对中国药企海外并购现状的描述统计和典型案例分析，总结经验，并提出对当前中国医药企业的海外并购策略。中国医药企业的海外并购应当在公司整体战略的指导下，基于各企业生命周期，选择是否海外并购以及合适的并购标的，同时区位上可以优先选择“一带一路”国家，并更加重视并购后整合。

Hydroxypropyl methylcellulose acetate succinate (HPMCAS) is a mixture of acetic acid and succinic acid esters of hydroxypropyl methyl cellulose so that it has an amphiphilic property. The glass transition temperature of HPMCAS is about 120 ℃. HPMCAS is commonly used as an enteric film-coating material because of its pH dependence. In recent years, the application researches of HPMCAS used as an amorphous solid dispersion carrier for poorly water soluble drugs are increasing. HPMCAS is suitable for use in common preparation methods of solid dispersions, such as solvent evaporation method, hot melt extrusion, spray (freeze) drying and milling method. Moreover, HPMCAS exhibits the ability of inhibit drug recrystallization in the processes of storage, in vitro dissolution and in vivo absorption of solid dispersions, which is beneficial for improving stability of solid dispersions. The progress of applications of HPMCAS to solid dispersions is reviewed in this paper.

(2S,3aS,7aS)-Octahydroindole-2-carboxylic acid benzyl p-toluenesulfonate(4) was obtained by catalytic hydrogenation and condensation-salification from (S)-indololine-2-carboxylic acid(2). Meanwhile, N-[(S) - 1-ethoxycarbonylbutyl]-(S)-alanine(6) was synthesized by one-step method with L-n-valine(5). Compound 4 reacted with compound 6 by condensation, hydrogenation and salt forming to give perindopril tert-butylamine salt(1). In the hydrogenation of 2, rhodium carbon was used as catalyst, and the reaction pressure was decreased from 5 MPa to 2.0 - 3.0 MPa, the reaction time was reduced from 40 h to 4 - 8 h, and the yield was 81％. In the last step, appropriate amount of water was added into hydrogenation solvent and the one-pot method of hydrogenation and salt formation was adopted, which could inhibit the formation of the impurity, ethyl (S)-2-[(3S,5aS,9aS,10aS)-3-methyl-1,4- dioxodecahydropyrazino[1,2-a]indol-2(1H)-yl]pentanoate(7), and the purity of 1 was 99.61％.

建立了在四参数回归计算法中，计算自由模型和平行曲线模型各参数点估计值的SAS 程序，以及标准品S 和供试品T 的相对效价及其置信区间估计的SAS 程序。结果显示，SAS 中的PROC NLIN 能够很好地给出四参数logistic 方程自由模型和平行曲线模型中各参数的点估计值，此外PROC IML 可以利用各参数的点估计值，以及输出数据集中各参数的标准误和协方差信息，计算标准品和供试品的相对效价和相对效价的95％置信区间。与Softmax 软件计算结果的相比较， SAS 能够给出几乎一致甚至更为精确的结果，从而证明了SAS 程序的可行性和适用性。SAS 能很好地被用于四参数回归计算法过程中。

The pramipexole dihydrochloride diphase sustained-release capsules were prepared by mixing two kinds of membrane-moderated pellets, which were coated with different layers by bottom spray fluid bed coating technology at certain proportion to obtain rapid- and sustained-release characteristics. The formulation was optimized by single factor experiment and central composite design-response surface methodology with the release similarity between self-made capsules and reference listed drug (Siforl) in pH 6.8 phosphate buffer (PBS). The results of validation test showed that the drug release behaviors of both preparations were similar in PBS or in pH 1.2 hydrochloric acid for first 1 or 2 h, followed by PBS, those similarity factor (f2) values were all above 50. In vivo pharmacokinetics of the self-made capsule and Siforl were investigated with Beagle dog model. The drug concentration in plasma was determined by LC-MS/MS, and pharmacokinetic parameters of these two formulations were calculated by non-compartmental model. The results showed that the self-made diphase phase sustainedrelease capsules and Siforl of cmax (1 118.3±121.9) and (1 108.6±183.2) pg/ml, AUC0→∞ (18 227.5±1 870.8) and (16 321.8±2 327.5)pg·ml-1·h, suggesting a similarity of these two preparations.

(S)-Naphthylglycidic ether [(S)-2] and (R)-3-(α-naphthoxy)-1,2-propanediol (5), the key chiral building block, were obtained with high enantiomeric excess by means of hydrolytic kinetic resolution (HKR) of naphthylglycidic ether (2) with (R,R)-Salen Co(Ⅲ)·BF3 complex (4), and then 5 was converted into (R)-2 by “one-pot” procedure which was developed with Sharpless. Optical pure compounds 2 were further transformed into corresponding (R)- and (S)-naftopidil by treatment with 1-(2-methoxyphenyl)piperizine (3), respectively. The enantiomeric excess of (R)- and (S)-naftopidil were both 98％.