枸橼酸他莫昔芬原料USP32标准(英文翻译)

Tamoxifen Citrate

C26H29NO·C6H8O7

Ethanamine, 2-[4-(1,2-diphenyl-1-butenyl)phenoxy]-N,N-dimethyl, (Z)-, 2-hydroxy-1,2,3-propanetricarboxylate (1:1).

(Z)-N,N-二甲基-2-[4-(1,2-二苯基-1-丁烯基)苯氧基]-乙胺枸橼酸盐

(Z)-2-[p-(1,2-Diphenyl-1-butenyl)phenoxy]-N,N-dimethylethylamine citrate (1:1) [54965-24-1].

» Tamoxifen Citrate contains not less than 99.0 percent and not more than 101.0 percent of C26H29NO·C6H8O7, calculated on the dried basis.

枸橼酸他莫昔芬 按干燥品计算，含C26H29NO·C6H8O7不得少于99.0%，不得多于101.0%。

Packaging and storage— Preserve in well-closed, light-resistant containers. 包装和贮存— 在密闭、耐光的容器中保存。

Description: White, fine, crystalline powder. Soluble in methanol; very slightly soluble in water, in acetone, in chloroform, and in alcohol. 性状：本品为白色结晶性粉末。

本品在甲醇中溶解，在水、丙酮、三氯甲烷和乙醇中极微溶解。 Melting Point: Melts at about 142°, with decomposition. 熔点：本品的熔点大约为142℃， 熔融时同时分解。 USP Reference standards <11>— USP Tamoxifen Citrate RS Identification—

563.

鉴别—

A: Infrared Absorption <197K>: a single band in the 1700 to 1740 cm-1 region of the spectrum.

红外吸收<197K>：显示1700 - 1740 cm-1区域的单波段。 B: Ultraviolet Absorption <197U>— 紫外吸收：

Solution: 20 µg per mL. 溶液：每毫升20微克。 Medium: methanol. 介质：甲醇

Loss on drying <731>— Dry it at 105℃ for 4 hours: it loses not more than 0.5% of its weight.

干燥失重<731>— 取本品，置105℃干燥4小时，减失重量不得过0.5%。 Residue on ignition <281>: not more than 0.2%. 炽灼残渣<281>: 不得高于0.2% Limit of E-isomer— E-异构限度—

Mobile phase— Prepare a methanol solution containing, in each liter, 320 mL of water, 2 mL of glacial acetic acid, and 1.08 g of sodium 1-octanesulfonate.

流动相—制备每升含有320毫升水、2毫升冰醋酸和1.08g辛烷磺酸钠的甲醇溶液。

Standard preparation— Dissolve a suitable quantity, accurately weighed, of USP Tamoxifen Citrate RS in Mobile phase to obtain a solution having a known concentration of about 600 µg per mL.

标准溶液—精密称取适量的枸橼酸他莫昔芬USP对照品，溶解于流动相中，以得到已知浓度为600µg/ mL的溶液。

Test preparation— Using about 30 mg of Tamoxifen Citrate, accurately weighed, proceed as directed under Standard preparation.

供试溶液— 取30 mg 枸橼酸他莫昔芬，精密称定，在标准溶液项指导下进行。

Chromatographic system (see Chromatography <621>)—The liquid

chromatograph is equipped with a 254-nm detector and a 4-mm × 30-cm column that contains packing L11. The flow rate is about 0.7 mL per minute. Chromatograph five replicate injections of the Standard preparation, and record the responses of the major peak: the relative standard deviation is not more than 3.0%, and the relative retention time of the minor E-isomer peak to that of the Z-isomer peak is not greater than 0.93.

色谱系统（见色谱技术<621>）—液相色谱仪的检测器波长为254nm，色谱柱型号

为4mm×30cm，填料为L11。流速约为0.7ml/min。将标准溶液5针重复进样进行色谱分析，并记录主峰响应值：相对标准偏差不大于3.0%，相对于Z异构峰的相对保留时间，E 异构次峰的相对保留时间不大于0.93.

Procedure— Separately introduce equal volumes (about 20 µL) of the Test preparation and the Standard preparation into the liquid chromatograph by means of a suitable sampling valve. Measure the minor peak responses for the E-isomer obtained from the Standard preparation and the Assay preparation. Calculate the quantity, in mg, of E-isomer (C26H29NO·C6H8O7) in the portion of Tamoxifen Citrate taken by the formula:

测定法— 分别将等体积（约20µL）的供试溶液和标准溶液通过合适的进样阀注入到液相色谱仪，测量标准溶液和含量测定溶液中E异构体的次峰响应值。按下式计算枸橼酸他莫昔芬中E 异构体（C26H29NO·C6H8O7）的量，以mg表示：

0.05C(rU / rS)

in which C is the concentration, in µg per mL, of the E-isomer as the citrate, based on its declared content in USP Tamoxifen Citrate RS in the Standard preparation, and the rU and rS are the minor peak responses obtained from the Assay preparation and the Standard preparation, respectively. The E-isomer content is not more than 0.3% of tamoxifen citrate (C26H29NO·C6H8O7).

式中: 基于USP枸橼酸他莫昔芬对照品对标准溶液的标示量，C表示枸橼酸E异构体的浓度（µg/ mL）; rU 和 rS 分别表示含量测定溶液与标准溶液中所测得的次峰响应值。E-异构体的含量不超过枸橼酸他莫昔芬(C26H29NO·C6H8O7)的0.3%。

Iron <241>— Accurately weigh 1.0 g, and transfer to a suitable crucible. Add sufficient sulfuric acid to wet the substance, and carefully ignite at a low temperature until thoroughly charred. (The crucible may be loosely covered with a suitable lid during the charring.) Add to the carbonized mass 2 mL of nitric acid and 5 drops of sulfuric acid, and heat cautiously until white fumes no longer are evolved. Ignite, preferably in a muffle furnace, at 500° to 600°, until the carbon is completely burned off. Cool, add 10 mL of warm 0.1 N hydrochloric acid, and digest for about 5 minutes. Transfer the contents of the crucible with the aid of small portions of water to a 50-mL volumetric flask, dilute with water to volume, and mix. Pipet 10 mL from the volumetric flask into a color-comparison tube, dilute with water to 45 mL, add 2 mL of hydrochloric acid, and mix. The limit is 0.005%.

铁<241>— 准确称取本品1.0克，置适宜的坩埚中，加适量的硫酸使湿润，低温小心灼烧，

直至全部炭化。（在炭化过程中坩埚不可盖严）。加2ml和硫酸5滴至炭化物上，小心加热直到白烟不再逸出，置马富炉中500~600℃灼烧， 直至完全灰化。放冷，加温的0.1N盐酸液10ml，加热5分钟。用少量水洗涤坩埚，洗液并入50-mL 量瓶中，用水稀释至

刻度，摇匀。从容量瓶中吸取10 mL移入比色管中，用水稀释至45 mL, 加2 mL 盐酸，并混匀。限度为0.005%。 Heavy metals, Method II <231>: 0.001%. 重金属，方法二<231>: 0.001%. Related impurities— 有关杂质—

Test preparation A— Disperse about 3 g in 100 mL of water in a separator. Over a 10-minute period add 50 mL of 0.5 N sodium hydroxide, with mixing. Extract with two 50-mL portions of ether, and combine the extracts. Wash with 20 mL of water, remove the water layer, and dry the ether layer over anhydrous sodium sulfate. Evaporate the ether layer under nitrogen, and dry in vacuum at room temperature for

2 hours. Accurately weigh 1.5 g of the residue into a 10-mL volumetric flask, add 5.0 mL of a mixture of 5 volumes of acetic anhydride and 95 volumes of pyridine, and heat at 60for 10 to 15 minutes. Cool, dilute with the same solvent mixture to volume, and mix.

供试溶液A— 取本品约 3g置分液漏斗中加水100ml。10分钟后，加0.5N

氢氧化钠溶液50ml混匀，用乙醚50ml提取两次，合并提取液。用水20ml洗脱，弃去水层，乙醚层用无水硫酸钠脱水。乙醚层置氮气下蒸发至干，室温下减压干燥2小时。精密称取残渣1.5g，置10ml量瓶中，加乙酸酐-吡啶混合液（5: 95）5.0ml，60℃加热10～15分钟。放冷，用上述混合液稀释至刻度，摇匀。

Test preparation B— Using the same acetic anhydride-pyridine mixture, prepare a 1:200 dilution of Test preparation A.

供试溶液B— 用上述乙酸酐-吡啶混合液稀释供试溶液A，1:200。 Chromatographic system (see Chromatography <621>)—Typically, the gas chromatograph is equipped with a flame-ionization detector, and contains a 4-mm × 1-m glass column packed with 5% liquid phase G17 on 100- to 120-mesh support S1AB conditioned at 300° for 24 hours. The column and injection port temperatures are maintained at about 260° and the detector temperature at about 300°. Dry helium is used as the carrier gas at a flow rate of about 60 mL per minute. In a suitable chromatogram, five replicate injections of Test preparation B show a relative standard deviation of not more than 3.0%.

色谱系统(见色谱法<621>)：气相色谱仪备有火焰-离子化检测器；

4-mm × 1-m玻璃管柱：涂布浓度为5%的G17(75%苯基-25%甲基聚硅氧烷)固定液，100～120目的S1AB(硅藻土：酸洗和碱洗)载体，300℃活化24小时。柱温与进样口温度约260℃，检测器温度约300℃。载气为干燥的氦气，流速60ml/min。供试溶液B重复进样5次的色谱中，相对标准偏差不得过3.0%。

Procedure— Inject equal portions (about 2 µL), accurately measured, of Test preparation A and Test preparation B into the chromatograph, and record the chromatograms from 0.1 to 5.0, relative to the retention time of the major peak. Measure the individual areas of the peaks other than those produced by the solvent and the tamoxifen on the chromatograms obtained from Test preparation A, and

calculate their sum. No single peak area is greater than the total area of the tamoxifen peak on the chromatogram obtained from Test preparation B (0.5%), and the sum of the peak areas is not greater than twice the total area of the tamoxifen peak on the chromatogram obtained from Test preparation B (1.0%).

测定法— 精密量取同体积(约2 µL)的供试溶液A与供试溶液B，注入色谱仪，记录相对于主峰的相对保留时间0.1～5.0色谱图，测量供试溶液A中除溶剂峰与他莫昔芬峰以外的峰面积，并计算这些峰的峰面积和。单个峰面积不得大于供试溶液B色谱图中他莫昔芬峰面积(0.5%)，总峰面积不得大于供试溶液B色谱图中他莫昔芬峰面积的2倍(1.0%)。

Assay— Weigh accurately about 1 g of Tamoxifen Citrate, and dissolve in 150 mL of glacial acetic acid. Titrate the solution with 0.1 N perchloric acid VS, determining the endpoint potentiometrically, using a glass indicator electrode and a silver-silver chloride reference electrode. Each mL of 0.1 N perchloric acid is equivalent to 56.36 mg of C26H29NO·C6H8O7.

含量测定— 精确称取1克枸橼酸他莫昔芬，并溶解于150毫升冰醋酸。 用0.1 N高氯酸滴定液滴定该溶液，确定端点电位，使用玻璃指示电极和银-氯化银参比电极。每毫升0.1 N高氯酸相当于56.36mg的C26H29NO·C6H8O7。

Auxiliary Information— Please check for your question in the FAQs before contacting USP. Topic/Question Contact Monograph Daniel K. Bempong, Ph.D. Senior Scientist 1-301-816-8143 Lili Wang, Technical Services Scientist 1-301-816-8129 RSTech@usp.org Expert Committee (MDPS05) Monograph Development-Pulmonary and Steroids Reference Standards

主题/问题 专著 联系 Daniel K. Bempong, Ph.D. Senior Scientist 1-301-816-8143 专家委员会 (MDPS05) 发展心血管专著 Monograph Development-Pulmonary and Steroids 引用标准 王莉莉，技术服务的科学家 1-301-816-8129 RSTech@usp.org

USP32–NF27 Page 3651

Chromatographic Column— TAMOXIFEN CITRATE

Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.