accurately

枸橼酸他莫昔芬原料USP32标准

TamoxifenCitrate

C

26

H

29

NO·C

6

H

8

O

7

563.64

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-dimethylethylaminecitrate(1:1)

[54965-24-1].

»TamoxifenCitratecontainsnotlessthan99.0percentandnotmorethan101.0

percentofC

26

H

29

NO·C

6

H

8

O

7

,calculatedonthedriedbasis.

枸橼酸他莫昔芬按干燥品计算，含C

26

H

29

NO·C

6

H

8

O

7

不得少于99.0%，不得多

于101.0%。

Packagingandstorage—Prerveinwell-clod,light-resistantcontainers.

包装和贮存—在密闭、耐光的容器中保存。

Description:White,fine,einmethanol;veryslightly

solubleinwater,inacetone,inchloroform,andinalcohol.

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。

MeltingPoint:Meltsatabout142°,withdecomposition.

熔点：本品的熔点大约为142℃，熔融时同时分解。

USPReferencestandards<11>—

USPTamoxifenCitrateRS

Identification—

鉴别—

A:InfraredAbsorption<197K>:asinglebandinthe1700to1740cm-1regionof

thespectrum.

红外吸收<197K>：显示1700-1740cm-1区域的单波段。

B:UltravioletAbsorption<197U>—

紫外吸收：

Solution:20µgpermL.

溶液：每毫升20微克。

Medium:methanol.

介质：甲醇

Lossondrying<731>—Dryitat105℃for4hours:itlosnotmorethan0.5%of

itsweight.

干燥失重<731>—取本品，置105℃干燥4小时，减失重量不得过0.5%。

Residueonignition<281>:notmorethan0.2%.

炽灼残渣<281>:不得高于0.2%

LimitofE-isomer—

E-异构限度—

Mobilepha—Prepareamethanolsolutioncontaining,ineachliter,320mLof

water,2mLofglacialaceticacid,and1.08gofsodium1-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。

Standardpreparation—Dissolveasuitablequantity,accuratelyweighed,ofUSP

TamoxifenCitrateRSinMobilephatoobtainasolutionhavingaknown

concentrationofabout600µgpermL.

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。

Testpreparation—Usingabout30mgofTamoxifenCitrate,accuratelyweighed,

proceedasdirectedunderStandardpreparation.

供试溶液—取30mg枸橼酸他莫昔芬，精密称定，在标准溶液项指导下进

行。

Chromatographicsystem(eChromatography<621>)—Theliquid

chromatographiquippedwitha254-nmdetectoranda4-mm×30-cmcolumnthat

tographfive

replicateinjectionsoftheStandardpreparation,andrecordtheresponsofthemajor

peak:therelativestandarddeviationisnotmorethan3.0%,andtherelativeretention

timeoftheminorE-isomerpeaktothatoftheZ-isomerpeakisnotgreaterthan0.93.

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—Separatelyintroduceequalvolumes(about20µL)oftheTest

preparationandtheStandardpreparationintotheliquidchromatographbymeansofa

etheminorpeakresponsfortheE-isomerobtained

atethequantity,in

mg,ofE-isomer(C26H29NO·C6H8O7)intheportionofTamoxifenCitratetakenby

theformula:

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)

inwhichCistheconcentration,inµgpermL,oftheE-isomerasthecitrate,badon

itsdeclaredcontentinUSPTamoxifenCitrateRSintheStandardpreparation,andthe

rUandrSaretheminorpeakresponsobtainedfromtheAssaypreparationandthe

Standardpreparation,-isomercontentisnotmorethan0.3%of

tamoxifencitrate(C

26

H

29

NO·C

6

H

8

O

7

).

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>—Accuratelyweigh1.0g,

sufficientsulfuricacidtowetthesubstance,andcarefullyigniteatalowtemperature

untilthoroughlycharred.(Thecruciblemaybeloolycoveredwithasuitablelid

duringthecharring.)Addtothecarbonizedmass2mLofnitricacidand5dropsof

sulfuricacid,,

preferablyinamufflefurnace,at500°to600°,untilthecarboniscompletelyburned

,add10mLofwarm0.1Nhydrochloricacid,anddigestforabout5minutes.

Transferthecontentsofthecruciblewiththeaidofsmallportionsofwatertoa

50-mLvolumetricflask,dilutewithwatertovolume,10mLfromthe

volumetricflaskintoacolor-comparisontube,dilutewithwaterto45mL,add2mL

ofhydrochloricacid,itis0.005%.

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）。加硝酸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10mL移入比色管中，用水稀释至45mL,加2mL

盐酸，并混匀。限度为0.005%。

Heavymetals,MethodII<231>:0.001%.

重金属，方法二<231>:0.001%.

Relatedimpurities—

有关杂质—

TestpreparationA—

a10-minuteperiodadd50mLof0.5Nsodiumhydroxide,twith

two50-mLportionsofether,th20mLofwater,

removethewaterlayer,anddrytheetherlayeroveranhydroussodiumsulfate.

Evaporatetheetherlayerundernitrogen,anddryinvacuumatroomtemperaturefor

telyweigh1.5goftheresidueintoa10-mLvolumetricflask,add5.0

mLofamixtureof5volumesofaceticanhydrideand95volumesofpyridine,and

heatat60,dilutewiththesamesolventmixturetovolume,

andmix.

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。

TestpreparationB—Usingthesameaceticanhydride-pyridinemixture,prepare

a1:200dilutionofTestpreparationA.

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。

Chromatographicsystem(eChromatography<621>)—Typically,thegas

chromatographiquippedwithaflame-ionizationdetector,andcontainsa4-mm×

1-mglasscolumnpackedwith5%liquidphaG17on100-to120-meshsupport

S1ABconditionedat300°umnandinjectionporttemperatures

aremaintainedatabout260°andthedetectortemperatureatabout300°.Dryhelium

table

chromatogram,fivereplicateinjectionsofTestpreparationBshowarelativestandard

deviationofnotmorethan3.0%.

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—Injectequalportions(about2µL),accuratelymeasured,ofTest

preparationAandTestpreparationBintothechromatograph,andrecordthe

chromatogramsfrom0.1to5.0,relativetotheretentiontimeofthemajorpeak.

Measuretheindividualareasofthepeaksotherthanthoproducedbythesolvent

andthetamoxifenonthechromatogramsobtainedfromTestpreparationA,and

lepeakareaisgreaterthanthetotalareaofthetamoxifen

peakonthechromatogramobtainedfromTestpreparationB(0.5%),andthesumof

thepeakareasisnotgreaterthantwicethetotalareaofthetamoxifenpeakonthe

chromatogramobtainedfromTestpreparationB(1.0%).

测定法—精密量取同体积(约2µL)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—Weighaccuratelyabout1gofTamoxifenCitrate,anddissolvein150

ethesolutionwith0.1NperchloricacidVS,

determiningtheendpointpotentiometrically,usingaglassindicatorelectrodeanda

of0.1Nperchloricacidis

equivalentto56.36mgofC

26

H

29

NO·C

6

H

8

O

7

.

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0.1N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0.1N高氯酸相当于56.36mg的C26H29NO·C6H8O7。

AuxiliaryInformation—PleacheckforyourquestionintheFAQsbefore

contactingUSP.

Topic/QuestionContactExpertCommittee

g,

Ph.D.

SeniorScientist

1-301-816-8143

(MDPS05)Monograph

Development-PulmonaryandSteroids

Reference

Standards

LiliWang,Technical

ServicesScientist

1-301-816-8129

RSTech@

主题/问题联系专家委员会

专著g,Ph.D.

SeniorScientist

1-301-816-8143

(MDPS05)发展心血管专著

MonographDevelopment-Pulmonary

andSteroids

引用标准王莉莉，技术服务的科学家

1-301-816-8129

RSTech@

USP32–NF27Page3651

ChromatographicColumn—TAMOXIFENCITRATE

Chromatographiccolumnstextisnotderivedfrom,andnotpartof,USP32orNF27.