藥分英文部分1.doc

緒論GLP (Good Laboratory Practice) 藥品非臨床研究質(zhì)量管理規(guī)范Good Laboratory Practice (GLP) deals with the organization, process and conditions under which laboratory studies are planned, performed, monitored, recorded and reported. GLP practices are intended to promote the quality and validity of test data.Published GLP regulations and guidelines have a significant impact on the daily operation of an analytical laboratory. GLP is a regulation. It is not only good analytical practice. Good analytical practice is important, but it is not enough. For example, the laboratory must have a specific organizational structure and procedures to perform and document laboratory work. The objective is not only quality of data but also traceability and integrity of data. But the biggest difference between GLP and Non-GLP work is the type and amount of documentation. For a GLP inspector it should be possible to look at the documentation and to easily find out who has done a study, how the experiment was carried out,which procedures have been used, and whether there has been any problem and if so how it has been solved. All routine work should follow written standard operating procedures (SOP). Facilities such as laboratories should be large enough and have the right construction to ensure the integrity of a study, for example, to avoid cross contaminationTest and control articles should have the right quality and instruments should be calibrated and well maintained People should be trained or otherwise qualified for the job Raw data and other data should be acquired, processed and archived to ensure integrity of data. GMP(Good Manufacture Practice) 藥品生產(chǎn)質(zhì)量管理規(guī)GMP refers to the Good Manufacturing Practice Regulations promulgated by the US Food and Drug Administration under the authority of the Federal Food, Drug, and Cosmetic ActThese regulations, which have the force of law, require that manufacturers, processors, and packagers of drugs, medical devices take proactive steps to ensure that their products are safe, pure, and effective. GMP regulations require a quality approach to manufacturing, enabling companies to minimize or eliminate instances of contamination, mixups, and errors.This in turn, protects the consumer from purchasing a product which is not effective or even dangerous. Failure of firms to comply with GMP regulations can result in very serious consequences including recall, seizure, fines, and jail time.GMP regulations address issues including recordkeeping, personnel qualifications, sanitation, cleanliness, equipment verification, process validation, and complaint handling. Most GMP requirements are very general and open-ended, allowing each manufacturer to decide individually how to best implement the necessary controls. GCP (Good Clinical Practice) 藥品臨床試驗(yàn)管理規(guī)范GCPGood Clinical Practice (GCP) is an international quality standard that is provided by International Conference on Harmonisation (ICH), an international body that defines standards, which governments can transpose into regulations for clinical trials involving human subjects.Good Clinical Practice guidelines include protection of human rights as a subject in clinical trial. It also provides assurance of the safety and efficacy of the newly developed compounds.Good Clinical Practice Guidelines include standards on how clinical trials should be conducted, define the roles and responsibilities of clinical trial sponsors, clinical research investigators, and monitors. In the pharmaceutical industry monitors are often called Clinical Research Associates.GAP(Good Agricultural Practice) 中藥材生產(chǎn)質(zhì)量管理規(guī)范AQC 分析質(zhì)量管理第十一章 吩噻嗪類抗精神病藥物的分析Perphenazine InjectionPerphenazine Injection is a sterile solution of Perphenazine in Water for Injection, prepared with the aid of Citric Acid. It contains not less than 90.0 percent and not more than 110.0 percent of the labeled amount of C21H26ClN3OS, as the citratePackaging and storage Preserve in single-dose or multiple-dose containers, preferably of Type I glass, protected from light.USP Reference standards USP Endotoxin RS. USP Perphenazine RS. NOTEThroughout the following procedures, protect test or assay specimens, the USP Reference Standard, and solutions containing them, by conducting the procedures without delay, under subdued light, or using low-actinic glassware. Identification Dilute 1 mL with methanol to 5 mL. Apply 5 L each of this solution and a solution of USP Perphenazine RS in methanol containing 1 mg per mL to a suitable thin-layer chromatographic plate, coated with a 0.25-mm layer of chromatographic silica gel. Develop the chromatogram in a solvent system consisting of a mixture of acetone and ammonium hydroxide (200:1) until the solvent front has moved about 15 cm. Air-dry the plate, and spray lightly with a solution of iodoplatinic acid prepared by dissolving 100 mg of chloroplatinic acid in 1 mL of 1 N hydrochloric acid, adding 25 mL of potassium iodide solution (4 in 100), diluting with water to 100 mL, and adding 0.50 mL of formic acid: the RF value of the principal spot obtained from the Injection corresponds to that obtained from the Standard solution. Bacterial endotoxins It contains not more than 35.7 USP Endotoxin Units per mg of perphenazine. pH : between 4.2 and 5.6. Other requirements It meets the requirements under Injections. Assay Acid-alcohol solution Transfer 10 mL of hydrochloric acid to a 1000-mL flask containing 500 mL of alcohol and 300 mL of water. Dilute with water to volume. Palladium chloride solution Dissolve 100 mg of palladium chloride in a mixture of 1 mL of hydrochloric acid and 50 mL of water in a 100-mL volumetric flask, heating on a steam bath to effect solution. Cool, dilute with water to volume, and mix. Store in an amber bottle and use within 30 days. On the day of use, transfer 50 mL to a 500-mL volumetric flask, add 4 mL of hydrochloric acid and 4.1 g of anhydrous sodium acetate, dilute with water to volume, and mix. Standard preparation Dissolve an accurately weighed quantity of USP Perphenazine RS in Acid-alcohol solution to obtain a solution having a known concentration of about 150 g per mL. Assay preparation Dilute 3.0 mL of Injection with Acid-alcohol solution to 100 mL in a volumetric flask. Procedure Mix 10.0 mL each of the Assay preparation and the Standard preparation with 15.0 mL of Palladium chloride solution, filter, if necessary, and concomitantly determine the absorbances of these solutions, against a reagent blank, in 1-cm cells at the wavelength of maximum absorbance at about 480 nm, with a suitable spectrophotometer. Calculate the quantity, in mg, of C21H26ClN3OS in the volume of Injection taken by the formula: 0.1C(AU / AS),in which C is the concentration, in g per mL, of USP Perphenazine RS in the Standard preparation, and AU and AS are the absorbances of the solutions from the Assay preparation and the Standard preparation, respectively 第9章 二氫吡啶類鈣通道阻滯劑的分析-雙語課程（Nifedipine ）C17H18N2O6 346.33 3,5-Pyridinedicarboxylic acid, 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-, dimethyl ester. Dimethyl 1,4-dihydro-2,6-dimethyl-4-(o-nitrophenyl)-3,5-pyridinedicarboxylate 21829-25-4. Nifedipine contains not less than 98.0 percent and not more than 102.0 percent of C17H18N2O6, calculated on the dried basis.Packaging and storage Preserve in tight, light-resistant containers. USP Reference standards USP Nifedipine RS. USP Nifedipine Nitrophenylpyridine Analog RS. USP Nifedipine Nitrosophenylpyridine Analog RS.NOTENifedipine, when exposed to daylight and certain wavelengths of artificial light, readily converts to a nitrosophenylpyridine derivative. Exposure to UV light leads to the formation of a nitrophenylpyridine derivative. Perform assays and tests in the dark or under golden fluorescent or other low-actinic light. Use low-actinic glassware. A: Infrared Absorption Do not dry specimens. B: Ultraviolet Absorption Spectral range: 450 to 200 nm. Solution To a 10-mL volumetric flask containing 14 mg of Nifedipine add 1.0 mL of chloroform, dilute with methanol to volume, and mix. Pipet a 1.0-mL aliquot of the solution into a 100-mL volumetric flask, dilute with methanol to volume, and mix. C: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay. Melting range, : between 171 and 175. Loss on drying Dry it at 105 to constant weight: it loses not more than 0.5% of its weight. Residue on ignition: not more than 0.1%, an ignition temperature of 600 being used. Heavy metals, Method II : 0.001%. Perchloric acid titration Transfer about 4 g of Nifedipine, accurately weighed, to a 250-mL conical flask, and dissolve in 160 mL of glacial acetic acid with the aid of an ultrasonic bath. Add 3 drops of p-naphtholbenzein TS, and titrate to a green endpoint with 0.1 N perchloric acid VS: not more than 0.12 mL of 0.1 N perchloric acid is consumed for each g of Nifedipine. Chloride and Sulfate To 5.0 g of Nifedipine in a 140-mL beaker add 4.0 mL of 6 N acetic acid and 46 mL of water. Bring carefully to a boil on a hot plate, cool, and filter through paper free of chloride and sulfate. Use this Nifedipine filtrate for the following tests. Chloride Pipet 2.5 mL of the Nifedipine filtrate into a 50-mL color-comparison tube, and add 12.5 mL of water. Into a matched color-comparison tube pipet 10 mL of a Standard solution containing 8.2 g of sodium chloride per mL corresponding to 5 g of chloride per mL, add 5.0 mL of water, and mix. To each tube add 0.15 mL of 0.3 M nitric acid and 0.3 mL of silver nitrate TS, and mix: the opalescence exhibited by the Nifedipine filtrate does not exceed that of the Standard solution (0.02%). Sulfate Pipet into each of two 50-mL matched color-comparison tubes 1.5 mL of sulfate solution consisting of sufficient potassium sulfate dissolved in water to obtain a sulfate concentration of 10 g per mL. To each tube add, successively and with continuous shaking, 0.75 mL of alcohol, 0.5 mL of a 6.1% aqueous solution of barium chloride, and 0.25 mL of 6 N acetic acid. Shake for an additional 30 seconds. Pipet into one tube, designated the Standard tube, 15 mL of the sulfate solution. Pipet into the other tube, designated the Specimen tube, 3 mL of the Nifedipine filtrate and 12 mL of water: the turbidity exhibited by the Specimen tube does not exceed that of the Standard tube (0.05%). 第十一章 抗生素類藥物的分析（Ampicillin ）C16H19N3O4S (anhydrous) 349.41Ampicillin is anhydrous or contains three molecules of water of hydration. It contains not less than 900 g and not more than 1050 g of C16H19N3O4S per mg, calculated on the dried basis.Packaging and storage Preserve in tight containers. Crystallinity : meets the requirements. Bacterial endotoxins Where the label states that Ampicillin is sterile or must be subjected to further processing during the preparation of injectable dosage forms, it contains not more than 0.15 USP Endotoxin Unit per mg of ampicillin.pH : between 3.5 and 6.0, in a solution containing 10 mg per mL. Water, Method I : not more than 2.0% where it is labeled as Ampicillin (anhydrous); between 12.0% and 15.0% where it is labeled as Ampicillin (trihydrate). AssayMobile phase Prepare a suitable filtered and degassed mixture of water, acetonitrile, 1 M monobasic potassium phosphate, and 1 N acetic acid (909:80:10:1). Make adjustments if necessary (see System Suitability under Chromatography). Diluent Mix 10 mL of 1 M monobasic potassium phosphate and 1 mL of 1 N acetic acid, dilute with water to 1000 mL, and mix. Standard preparation Dissolve a suitable quantity of USP Ampicillin RS, accurately weighed, in Diluent to obtain a solution having a known concentration of about 1 mg per mL, using shaking and sonication, if necessary, to achieve complete dissolution. Use this solution promptly after preparation. Assay preparation Transfer an accurately weighed quantity of Ampicillin, equivalent to about 100 mg of anhydrous ampicillin, to a 100-mL volumetric flask, add about 75 mL of Diluent, shake and sonicate, if necessary, to achieve complete dissolution, dilute with Diluent to volume, and mix. Use this solution promptly after preparation.Chromatographic system (see Chromatography) The liquid chromatograph is equipped with a 254-nm detector, a 4-mm 5-cm pre-column containing 5- to 10-m packing L1, and a 4-mm 30-cm analytical column containing 5- to 10-m packing L1. The flow rate is about 2 mL per minut第十二章 喹啉與青蒿素類抗瘧藥物的分析（Quinine Sulfate ）(C20H24N2O2)2H2SO42H2O 782.94Cinchonan-9-ol, 6-methoxy-, (8a,9R)-, sulfate (2:1) (salt), dihydrate. Quinine sulfate (2:1) (salt) dihydrate 6119-70-6. Quinine Sulfate is the sulfate of an alkaloid obtained from the bark of species of Cinchona. It contains not less than 99.0 percent and not more than 101.0 percent of total alkaloid salt, calculated as (C20H24N2O2)2H2SO4, on the anhydrous basis.Packaging and storage Preserve in well-closed, light-resistant containers. USP Reference standards USP Quinine Sulfate RS. USP Quininone RS. Identification A: A 1 in 2000 solution in dilute sulfuric acid (1 in 350) exhibits a vivid blue fluorescence. On the addition of a few drops of hydrochloric acid, the fluorescence disappears. B: In the test for Chromatographic purity, the RF value of the principal spot obtained from the Test preparation corresponds to that from the Standard preparation. C: A solution (1 in 50) made with the aid of a few drops of hydrochloric acid responds to the tests for Sulfate. Specific rotation: between -235 and-245 . Test solution: 20 mg per mL, in 0.1 N hydrochloric acid. Water, Method : between 4.0% and 5.5%. Residue on ignition: not more than 0.1%. Heavy metals, Method II : 0.001%.Chloroform-alcohol-insoluble substances Warm 2 g with 15 mL of a mixture of chloroform and dehydrated alcohol (2:1) at about 50 for 10 minutes. Filter through a tared, sintered-glass filter, using gentle suction. Wash the filter with five 10-mL portions of the chloroform-alcohol mixture, dry at 105 for 1 hour, and weigh: the weight of the residue does not exceed 2 mg (0.1%). Chromatographic purityStandard preparation Prepare a solution of USP Quinine Sulfate RS in diluted alcohol to contain 6 mg per mL. Diluted standard preparation Dilute a portion of the Standard preparation with diluted alcohol to a concentration of 0.06 mg per mL. Related substances preparation Prepare a solution in diluted alcohol containing in each mL 0.05 mg each of USP Quininone RS (corresponding to 0.06 mg of the sulfate), and 0.10 mg of cinchonidine (corresponding to 0.12 mg of the sulfate). solution of Test preparation Prepare a Quinine Sulfate in diluted alcohol to contain 6 mg per mL. Procedure Apply 10-L portions of the Test preparation, the Standard preparation, the Diluted standard preparation, and the Related substances preparation to a suitable thin-layer chromatographic plate (see Chromatography) coated with a 0.25-mm layer of chromatographic silica gel. Allow to dry, and develop the chromatogram in a solvent system consisting of a mixture of chloroform, acetone, and diethylamine (5:4:1), the solvent chamber being used without previous equilibration. When the solvent front has moved about 15 cm, remove the plate from the chamber, mark the solvent front, and allow the solvent to evaporate. Spray the chromatogram with glacial acetic acid. Locate the spots on the plate by examination under long-wavelength UV light. Any spot produced by the Test preparation at the RF value of a spot produced by the Related substances preparation is not greater in size or intensity than that corresponding spot. Apart from these spots and from the spot appearing at the RF value of Quinine Sulfate, any additional fluorescent spot is not greater in size or intensity than the spot of the Diluted standard preparation. Spray the plate with potassium iodoplatinate TS. Any spot produced by the Test preparation is not greater in size or intensity than a corresponding spot from the Related substances preparation. 第十三章 莨菪烷類抗膽堿藥物的分析 （Atropine Sulfate Injection） Atropine Sulfate Injection is a sterile solution of Atropine Sulfate in Water for Injection. It contains not less than 93.0 percent and not more than 107.0 percent of the labeled amount of (C17H23NO3)2H2SO4 H2O.Packaging and storage Preserve in single-dose or in multiple-dose containers, preferably of Type I glass. USP Reference standards USP Atropine Sulfate RS. USP Endotoxin RS. Identification (see Thin-Layer Chromatographic Identification Test) Adsorbent: chromatographic silica gel. Developing solvent: mixture of chloroform and diethylamine (9:1). Test preparation Use undiluted. Apply 15 L. Detection reagent: potassium iodoplatinate TS. Procedure Proceed as directed for Procedure under Thin-Layer Chromatographic Identification Test, the spots on the plate located by spraying with Detection reagent. Bacterial endotoxins It contains not more than 55.6 USP Endotoxin Units per mg of atropine sulfate. pH: between 3.0 and 6.5. Other requirements It meets the requirements under Injections. Assay Acetate buffer Prepare a solution in water containing in each L 0.05 mole of sodium acetate and 2.9 mL of glacial acetic acid. Mobile phase Transfer 5.1 g of tetrabutylammonium hydrogen sulfate to a 1-L volumetric flask, add 50 mL of acetonitrile, and dilute with Acetate buffer to volume. Adjust with 5 N sodium hydroxide to a pH of 5.5 0.1.Standard preparation Dissolve an accurately weighed quantity of USP Atropine Sulfate RS in water, and dilute quantitatively with water to obtain a solution having a known concentration of about 80 g p