Gemcitabine Hydrochloride CAS 122111-03-9 API USP35 Standard

Gemcitabine Hydrochloride
C9H11F2N3O4·HCl 299.66
Cytidine, 2′-deoxy-2′,2′-difluro-, monohydrochloride.
I-2'-Deoxy-2′, 2′-difluorocytidine monohydrochloride (β-isomer) [122111-03-9].
» I-Gemcitabine Hydrochloride iqulethe ngaphantsi kweepesenti ze-97.5 kwaye ingabi ngaphezu kwe-101.5 ipesenti ye-C9H11F2N3O4·HCl, ibalwa ngokwesiseko.
[Isilumkiso-Gemcitabine Hydrochloride yi-agent ye-cytotoxic enamandla.Kufuneka kuthathwe ngononophelo olukhulu ukuthintela ukuphefumla amasuntswana kunye nokubeka ulusu kuwo.]
Ukupakishwa kunye nokugcinwa-Londoloza kwizikhongozeli eziqinileyo.
Ukuleyibhile-Apho ilungiselelwe ukusetyenziswa ekulungiseleleni iifom zedosi etofwayo, ileyibhile ichaza ukuba ayinyumba okanye kufuneka ixhomekeke ekuqhubekeni phambili nokusetyenzwa ngexesha lolungiselelo lweefom zesitofu esitofwayo.
Imigangatho yezalathiso ye-USP <11>-
USP Cytosine RS
USP Endotoxin RS
USP Gemcitabine Hydrochloride RS
Isazisi-
A: I-Infrared Absorption <197K>.
B: Iyahlangabezana neemfuno zeemvavanyo zeChloride <191>.
Ukujikeleza okuthe ngqo <781S>: phakathi kwe +43 kunye +50, kwi-20.
Isisombululo sovavanyo: 10 mg nge-mL nganye.
pH <791>: phakathi kwe-2.0 kunye ne-3.0, kwisisombululo esiqulethe i-10 mg nge-mL.
Intsalela ekutshisweni <281>: hayi ngaphezulu kwe-0.1%.
Iintsimbi ezinzima, Indlela I <231>: 0.001%.
Ukucoceka kweChromatographic-
Isisombululo A- Qhuba njengoko kuqondiswe kwisigaba se-Mobile kwi-Assay.
Isisombululo B-Lungisa i-methanol ehluziweyo kunye ne-degassed.
Isigaba seselula-Sebenzisa imixube eguquguqukayo yeSisombululo A kunye neSisombululo B njengoko kuyalelwe phantsi kweChromatographic system.Yenza uhlengahlengiso, ukuba kuyimfuneko (jonga ukufaneleka kweNkqubo phantsi kweChromatography 621).
Isisombululo sokufaneleka kwenkqubo-Qhuba njengoko kuyalelwe kuVavanyo.
Isisombululo esisemgangathweni-Dibanisa isixa esilinganiswe ngokuchanekileyo se-USP Gemcitabine Hydrochloride RS kunye ne-USP Cytosine RS emanzini, kwaye nciphisa ngokobungakanani, kwaye ngokwenyathelo xa kuyimfuneko, ukufumana isisombululo esinoxinzelelo olwaziwayo malunga ne-2 µg ngemL nganye.
Isisombululo sovavanyo-Ukudlulisa malunga ne-50 mg ye-Gemcitabine Hydrochloride, ilinganiswe ngokuchanekileyo, kwi-flask ye-volumetric ye-25-mL, inyibilika kwaye ihlanjululwe ngamanzi ukuya kwivolumu, kwaye udibanise.
Inkqubo yeChromatographic (jonga i-Chromatography 621) -Qhubeka njengoko kuyalelwe phantsi kwe-Assay.Ichromatograph icwangciswe ngolu hlobo lulandelayo.
Ixesha (imizuzu) Isisombululo A (%) Isisombululo B (%) Uvavanyo
0–8 97 3 isokhrasi
8–13 97®50 3®50 umyinge womda
13–20 50 50 isokhrasi
20–25 50®97 50®3 ulungelelwaniso kwakhona
I-Chromatograph isisombululo sokufaneleka kweSistim, kwaye urekhode iimpendulo eziphezulu njengoko ziqondiswe kwiNkqubo: amaxesha okugcinwa okuhambelanayo malunga ne-0.5 ye-gemcitabine -anomer kunye ne-1.0 ye-gemcitabine;isisombululo, R, phakathi kwe-gemcitabine -anomer kunye ne-gemcitabine ayikho ngaphantsi kwe-8.0;kwaye i-tailing factor ye-gemcitabine ayikho ngaphezu kwe-1.5.I-Chromatograph isisombululo soMgangatho, kwaye urekhode iimpendulo eziphezulu njengoko ziqondiswe kwiNkqubo: amaxesha okugcinwa okuhambelanayo malunga ne-0.1 ye-cytosine kunye ne-1.0 ye-gemcitabine;ukutenxa komgangatho ozalanayo wokuphindaphinda iinaliti akukho ngaphezu kwe-2.0%.
Inkqubo-Ngokwahlukileyo tofa umthamo (malunga nama-20 µL) wesisombululo esiPhakathi kunye nesisombululo soVavanyo kwichromatograph, urekhode ichromatogram, kwaye ulinganise zonke iimpendulo eziphakamileyo.Bala ipesenti ye-cytosine kwisahlulo seGemcitabine esithathwe ngefomula:
2.5(Cc / W)(rt / rs)
apho i-Cc ikuxinzelelo lwe-USP Cytosine RS kwisisombululo esiseMgangathweni, kwi-µg nge-mL;W bubunzima, ngo-mg, weGemcitabine ethathiweyo;rt yincopho impendulo cytosine kwi Uvavanyo isisombululo;kunye ne-rs yimpendulo ye-cytosine kwisisombululo esiPhakathi: akukho ngaphezu kwe-0.1% ye-cytosine efunyenweyo.Bala ipesenti yokungahlambuluki ngakunye ngaphandle kwe-cytosine kwisahlulo seGemcitabine esithathwe ngefomula:
2.5(Cs / W)(ri / rs)
apho i-Cs iluxinzelelo lwe-USP Gemcitabine Hydrochloride RS kwisisombululo esiPhakathi, kwi-µg nge-mL;W bubunzima, ngo-mg, weGemcitabine ethathiweyo;ri yincopho impendulo yokungcola nganye kwisisombululo Test;kunye ne-rs yimpendulo ngenxa ye-gemcitabine kwisisombululo soMgangatho: akukho ngaphezu kwe-0.1% ye-gemcitabine -anomer okanye nayiphi na enye into engcolileyo efunyenweyo;kwaye isimbuku sabo bonke ukungcola akukho ngaphezu kwe-0.2%.Kungabandakanyi isimbuku sabo bonke ukungcola naziphi na iincopho ezingaphantsi komda wobungakanani (0.02%).
Ezinye iimfuno-Apho ileyibhile ichaza ukuba i-Gemcitabine Hydrochloride iyinyumba, ihlangabezana neemfuno ze-Bacterial endotoxins kunye ne-Sterility phantsi kwe-Gemcitabine ye-Injection.Apho ileyibhile ichaza ukuba i-Gemcitabine Hydrochloride kufuneka ihlaziywe ngokuqhubekayo ngexesha lokulungiswa kweefom ze-injectable dosage, ihlangabezana neemfuno ze-Bacterial endotoxins phantsi kwe-Gemcitabine ye-Injection.
Isivavanyi-
Isigaba seselula-Lungisa isisombululo esihluziweyo kunye ne-degassed equkethe i-13.8 g ye-monobasic sodium phosphate kunye ne-2.5 mL ye-phosphoric acid kwi-1000 mL yamanzi.[Qaphela-I-pH yesi sisombululo iphakathi kwe-2.4 kunye ne-2.6.]
Isisombululo sokufaneleka kwenkqubo-Ukudlulisa malunga ne-10 mg ye-Gemcitabine Hydrochloride kwi-vial encinci, yongeza i-4 mL yesisombululo esiqulethe i-168 mg ye-potassium hydroxide nge-mL ye-methanol, i-cap tightly, kunye ne-sonicate.Ukushisa kwi-55 kwii-6 kwiiyure ze-16, vumela ukupholisa, kwaye uthumele iziqulatho kwi-flask ye-volumetric ye-100-mL ngokuhlamba okulandelelanayo kwe-1% (v / v) i-phosphoric acid.Nciphisa nge-1% ye-phosphoric acid kwivolumu, kwaye udibanise.[Qaphela-Esi sisombululo siqulathe malunga ne-0.02 mg nge-mL nganye ye-gemcitabine α-anomer.]
Ukulungiswa okusemgangathweni-Dibanisa isixa esilinganiswe ngokuchanekileyo se-USP Gemcitabine Hydrochloride RS emanzini, kwaye unciphise ngokomlinganiselo, kwaye ulandele inyathelo xa kuyimfuneko, ngamanzi ukuze ufumane isisombululo esinoxinzelelo olwaziwayo malunga ne-0.1 mg nge-mL.
Ukulungiswa kwe-Assay-Transfer malunga ne-20 mg ye-Gemcitabine Hydrochloride, ilinganiswe ngokuchanekileyo, kwi-flask ye-volumetric ye-200-mL, inyibilika kwaye ihlanjululwe ngamanzi ukuya kumthamo, kwaye udibanise.
Inkqubo yeChromatographic (jonga i-Chromatography <621>)-I-chromatograph yolwelo ixhotyiswe nge-275-nm detector kunye ne-4.6-mm × 25-cm ikholamu equlethe i-5-µm yokupakisha i-L7.Izinga lokuhamba malunga ne-1.2 mL ngomzuzu.I-Chromatograph isisombululo sokufaneleka kweNkqubo, kwaye urekhode iimpendulo eziphezulu njengoko ziqondiswe kwiNkqubo: isisombululo, R, phakathi kwe-gemcitabine -anomer kunye ne-gemcitabine ayikho ngaphantsi kwe-8.0;kwaye into yomsila egqitywe kwi-gemcitabine ayikho ngaphezu kwe-1.5.I-Chromatograph Ukulungiswa koMgangatho, kwaye urekhode iimpendulo eziphakamileyo njengoko ziqondiswe kwiNkqubo: ukutenxa komgangatho ohambelanayo we-replicate injection ayikho ngaphezu kwe-1.0%.
Inkqubo-Ngokwahlukileyo tofa imithamo elinganayo (malunga nama-20 µL) yolungiselelo loMgangatho kunye nolungiselelo loVavanyo kwichromatograph, urekhode iichromatogram, kwaye ulinganise iimpendulo zeencopho ezinkulu.Bala ubuninzi, kwi-mg, ye-C9H11F2N3O4 · HCl kwisahlulo seGemcitabine Hydrochloride ethathwe ngefomula:
200C(rU / rS)
apho i-C igxininise, kwi-mg nge-mL, ye-USP Gemcitabine Hydrochloride RS kulungiselelo oluMgangatho;kunye ne-rU kunye ne-rS yincopho yeempendulo ezifunyenwe kulungiselelo loVavanyo kunye nolungiselelo loMgangatho, ngokulandelelanayo.