Tirzepatide impurities

Tirzepatide Impurities|Tilpeptide Impurity Tswj|Impurity Custom Synthesis thiab Structure Confirmation|Kev tshawb fawb-Peptide

Tirzepatide Impurities tswj - rau GLP-1/GIP dual-lub hom phiaj kev tshawb fawb tshuaj zoo, kev qhia tshuaj generic.Science-Peptide muab kev cai synthesis ntawm tilpeptide-txog impurities, suav nrog kev tshem tawm peptides, oxidized impurities, fatty aciders exfoliation, thiab lwm yam. Peb tuaj yeem pab txhawb koj txoj kev kawm impurity spectroscopy nrog cov ntaub ntawv pom zoo. Txais tos tiv tauj peb.

Tirzepatide (Tirzepatide) yog GLP-1/GIP dual agonist uas Eli Lilly tuaj nrog, thiab nws tau ua tiav puv ob xyoos no. Nws muaj cov txiaj ntsig zoo ntawm kev txo cov suab thaj thiab muaj zog ntawm kev txo qhov hnyav, thiab hu ua kev hloov kho tshiab ntawm "cov tshuaj muaj txiaj ntsig zoo rau kev poob phaus". Cov neeg tsim khoom hauv tsev ntawm peptide generic tshuaj, ntau tus tab tom saib nws - tom qab tas sij hawm ntawm patent, leej twg tuaj yeem ua ntej los ntawm kev tshawb fawb zoo, leej twg yuav muaj lub sijhawm los tuav thawj generic.

 

Txawm li cas los xij, qhov zoo ntawm tilpeptide tsis yog qhov yooj yim rau kev kawm. Nws yog qhov nyuaj dua li simethicone, nrog 39 amino acids, fatty acid side chain (eicosanedioic acid) thiab ib qho txuas. Cov impurities uas yuav tshwm sim thaum lub sij hawm synthesis yog ntau dua li cov peptides zoo tib yam. Tsis muaj peptides, oxidative impurities, fatty acid shedding khoom, dimers, linker-txog impurities txhua tus yuav tsum muaj kev tswj, txhua tus yuav tsum tau meej.

 

Peb tau sau ntau qhov kev paub dhau los hauv kev sib xyaw ntawm cov peptide impurities complex. Peb tau tshwj xeeb hauv kev tshawb fawb ntawm tilpeptide, thiab peb paub tias dab tsi yog qhov teeb meem ntawm nws cov impurity profile thiab dab tsi yog qhov tseem ceeb tswj cov khoom. Peb tuaj yeem hloov kho cov kev sib txuas ntawm ntau yam tilpeptide impurity tswj raws li koj xav tau, nrog cov ntaub ntawv lees paub cov qauv, thiab pab koj tsim txoj hauv kev kom koj yuav tsis tshua muaj kev tshaj tawm ntxiv thaum ua ntawv.

Cov qauv molecular ntawm tilpeptide txiav txim siab tias nws cov impurity profile yog qhov nyuaj dua li cov peptides dav dav. Thaum peb ua cov kev tshawb fawb impurity, peb feem ntau tsom rau cov pawg no:

Peptide ploj lawm
Lub 39 amino acids, ib qho ntawm ib qho uas tsis tau thaum lub sij hawm tsim cov txheej txheem, yog ib qho impurity. Lub sijhawm khaws cia ntawm peptides uas ploj lawm ntawm HPLC tau nthuav dav, nrog cov polarity sib txawv ntawm cov peptides uas ploj lawm hauv ntau txoj haujlwm. Qee qhov ploj lawm ntawm N-terminus, qee qhov ntawm nruab nrab, thiab qee qhov ze ntawm qhov chaw fatty acid txuas. Peb tau txais kev txiav txim los ntawm ib tus neeg siv khoom rau 15 peptides uas ploj lawm nyob rau hauv ntau txoj haujlwm los txheeb xyuas tag nrho cov khoom tsis huv uas ploj lawm hauv lawv cov txheej txheem.

Oxidizing impurities
Kev sib ntsib ntawm tilpeptide yog raug rau oxidation rau sulfoxide thiab tom qab ntawd rau sulfone. Oxidized impurities feem ntau tshwm sim hauv kev tshawb fawb kev ruaj ntseg thiab loj hlob tom qab lub sijhawm. Peb tau ua qhov sib piv, nyob rau hauv cov xwm txheej ceev rau ib hlis, oxidation ncov tuaj yeem loj hlob mus rau ntau dua 0.3%, tsis muaj kev tswj hwm.

Fatty acid shedding cov khoom
Qhov no yog ib qho impurity tshwj xeeb rau tilpeptide. Nws cov roj fatty acid sab saw (eicosanedioic acid) yog txuas rau lysine los ntawm kev sib txuas, thiab qhov kev hloov kho no yuav raug tshem tawm ib nrab thaum lub sijhawm sib txuas lossis khaws cia, uas ua rau muaj cov roj fatty acid- tshem tawm cov impurities. Qhov teeb meem ntau dua, qhov tso tawm tuaj yeem tshwm sim ntawm qhov chaw sib txawv - nruab nrab ntawm fatty acid thiab tus linker, los yog nruab nrab ntawm cov linker thiab peptide - ua rau cov impurities sib txawv. Peb tau tsim ntau cov roj fatty acid-txog impurities rau peb cov neeg siv khoom, xws li los ntawm kev ua tiav los ntawm ib qho me me.

Dimers/polymers
Ob lossis ntau dua tilpeptide molecules pawg ua ke los tsim ib qho dimer lossis siab dua. Qhov hnyav molecular ntawm lub dimer yog ob npaug ntawm lub ntsiab ncov, thiab feem ntau nws yog qhov dav dav ntawm HPLC, yog li nws yuav tsum tau muab cais tshwj xeeb thiab ua kom huv si ua ntej nws tuaj yeem siv los tswj. Peb tau ua tiav qhov kev npaj ntawm dimers, thiab nws tau siv ntau qhov kev ua kom huv huv kom ua tiav qhov purity ntau dua 95%.

Linker-txog impurities
Kev hloov pauv fatty acid ntawm tilpeptide siv cov linker (piv txwv li, -Glu, PEG, thiab lwm yam), thiab tus linker no nws tus kheej tuaj yeem tsim cov kev cuam tshuam sab nraud thaum lub sijhawm sib txuas, tsim cov impurities nrog cov txuas uas ploj lawm lossis tsis tiav. Hom impurity no tsis pom muaj nyob rau hauv cov peptides, tab sis yog tshwj xeeb rau tilpeptide, uas yuav tsum tau kawm tshwj xeeb.

Deamidated impurities
Asparagine (Asn) thiab glutamine (Gln) tau yooj yim deamidated nyob rau hauv acidic los yog cua sov tej yam kev mob, ua rau isomers. Muaj ob peb Asn thiab Gln nyob rau hauv qhov sib lawv liag ntawm tilpeptide, thiab cov deamidation impurity feem ntau tshwm nyob rau hauv qhov yuam kev degradation test, yog li cov khoom tswj yuav tsum tau siv los nrhiav cov impurity.

Diastereoisomers
Thaum lub sij hawm ntev saw synthesis, ib tug neeg amino acids yuav undergo racemization, ua rau diastereoisomers. Cov ntsiab lus ntawm hom impurity no feem ntau tsis siab, tab sis cov kws tshaj lij yuav nug thaum tshaj tawm, thiab nws yog qhov zoo dua kom muaj cov khoom tswj kom paub meej.

Ntau yam ntawm cov impurities no tsis tuaj yeem yuav thiab yuav tsum tau ua raws li kev cai. Peb tau ua ntau txoj haujlwm ntawm kev hloov kho ntawm tilpeptide impurities, npog tag nrho cov pawg saum toj no.

Kev tshem tawm ntawm peptide series
We synthesize whatever is missing. For example, the lysine at position 20 is missing, or the amino acid near the fatty acid attachment site is missing. We will synthesize according to your process impurity profile, and the purity is usually >95%, nrog MS thiab NMR kev pom zoo. Peb tau tsim cov peptides nrog 5 amino acid sib nrug los ntawm N-terminal mus rau C-terminal.

Oxidizing impurities
Met in Tilpeptide is oxidized to sulfoxide or sulfone, and we can control the oxidation conditions and synthesize the oxidized control product. We can control the oxidation conditions and synthesize the oxidized control. The purity is >95% thiab peb tuaj yeem muab LC-MS spectrum kom paub meej tias qib oxidation. Sulfoxide thiab sulfone raug cais los ntawm HPLC, thiab peb tuaj yeem ua ob qho tib si.

Fatty acid shedding cov khoom
Qhov no yog ib qho nyuaj tshaj plaws impurities ua hauj lwm nrog tilpeptide. Cov saw roj fatty acid tuaj yeem raug tshem tawm tag nrho, lossis nws yuav raug tshem tawm (xws li ob peb carbons dhau los lawm). Peb tuaj yeem tsim cov qauv sib txawv rau ntau txoj haujlwm ntawm cov saw hlau. Nyob rau hauv ib qho ntawm cov haujlwm nyuaj tshaj plaws uas peb tau ua, tus neeg siv khoom thov kom peb muab cov impurity nrog 8 carbons uas ploj lawm los ntawm fatty acid saw, thiab nws tau siv ob lub hlis los ua kom nws zoo.

Dimer
Dimers tsim los ntawm tus ntoo khaub lig-txuas los yog tsis yog-covalent kev sib cuam tshuam tuaj yeem npaj tau los ntawm ntau txoj hauv kev thiab cais tawm thiab ua kom huv huv los muab kev tswj hwm purity siab. Dimers muaj zog heev los ntxuav, tab sis peb muaj kev paub paub yuav ua li cas cais cov monomers.

Linker-txog impurities
Tus linker ( -Glu, PEG, thiab lwm yam) tej zaum yuav ploj los yog tsis tiav, ua rau muaj kev cuam tshuam ntawm impurities. Peb tuaj yeem ua ke ntau yam sib txawv nrog cov txuas uas ploj lawm, cov txuas txuas luv luv, lossis cov sib txuas tsis sib xws, thiab pab koj tsim cov spectra ntawm cov impurities.

Deamidated impurities
Rau qhov chaw Asn thiab Gln nyob rau hauv ib theem zuj zus, peb tuaj yeem npaj deamidated impurity tswj los ntawm kev quab yuam degradation los yog tsom synthesis. Qhov sib txawv ntawm qhov hnyav ntawm molecular tom qab deamidation tsuas yog 1, uas tsis yooj yim rau qhov txawv ntawm MS, yog li peb feem ntau siv NMR lossis tshwj xeeb chromatographic mob kom paub meej.

Lwm yam customized impurities
Yog tias koj pom qhov tsis paub tsis meej tshiab hauv koj qhov kev tshawb fawb, peb tuaj yeem pab koj txheeb xyuas cov qauv thiab sib txuas nws. Xa peb cov qauv, peb yuav ua LC-MS tsom xam, txiav cov qauv, tom qab ntawd cov kev taw qhia kev sib txuas, thiab tom qab ntawd sib piv lub sijhawm khaws cia thiab huab hwm coj ntau kom paub meej qhov kev pom zoo. Peb tau ua cov txheej txheem no ntau zaus thiab qhov kev vam meej yog siab heev.

analytical method development thiab validation
Thaum teeb tsa HPLC lossis LC-MS txoj kev, yuav tsum muaj kev tswj hwm qhov tsis huv rau hauv cheeb tsam, kev txiav txim siab ntawm kev sib cais, kev txheeb xyuas cov kab ntau thiab rov qab. Yog tsis muaj kev tswj, txoj kev validation yog ploj lawm ib daim. Ntau tus neeg muas zaub hais kom peb ua ob peb qhov tseem ceeb impurities ua ntej los teeb tsa txoj kev, thiab tom qab ntawd maj mam ua qhov seem.

Heterogeneous pawg spectrometry
Thaum cov tshuaj generic tau tshaj tawm, yuav tsum tau ua kom tiav cov txiaj ntsig zoo thiab kev soj ntsuam ntau ntawm cov txheej txheem impurities thiab degradation khoom. Qhov chaw, cov ntsiab lus thiab cov qauv ntawm txhua qhov impurity yuav tsum tau lees paub los ntawm kev tswj cov khoom. Peb tau pom daim ntawv tshaj tawm ntawm cov ntaub ntawv raug xa mus rau hauv, cuaj zaug ntawm kaum yog cov impurities ntawm daim ntawv no tsis nkag siab.

Kev tshawb fawb txog kev ruaj ntseg
Nyob rau hauv lub sij hawm ntev - kev ruaj ntseg thiab ceev cov kev ntsuam xyuas, nws yog ib qho tsim nyog los txiav txim siab seb cov khoom degradation twg yog qhov tseem ceeb thiab qhov sib txawv ntawm cov ntsiab lus yog dab tsi. Nrog rau kev tswj impurity, peb tuaj yeem ua kom muaj nuj nqis thiab saib xyuas. Ib tus neeg siv khoom tau ua qhov kev ruaj ntseg ntawm kev npaj tilpeptide, thiab pom tias qhov degradation ncov loj hlob sai heev nyob rau hauv cov xwm txheej ceev, yog li peb tau soj ntsuam thiab ua kom nws los ntawm MS kom paub meej cov qauv, thiab tom qab ntawd cov neeg siv khoom tau txais kev tso siab los qhia nws.

Batch tso tawm xeem
Tom qab kev lag luam, txhua pawg ntawm API lossis cov qauv yuav tsum tau kuaj xyuas cov khoom hauv nqe lus nug. Kev tswj hwm impurity yog cov cuab yeej tseem ceeb rau kev sim tso tawm.

Cov ntaub ntawv hais txog cov ntawv tshaj tawm tshuaj generic
Kev tshawb fawb impurity yog ib feem tseem ceeb ntawm cov ntaub ntawv ua ntaub ntawv. Muab tag nrho impurity profileing thiab tswj cov ntaub ntawv ua rau txo qis kev pheej hmoo ntawm kev tshuaj xyuas kev tso tawm.

Case 1: lub tuam txhab kws tshuaj, tilpeptide generic drug program
Lawv tab tom tsim ib qho kev hloov pauv dav dav ntawm tilpeptide thiab xav tau cov txheej txheem ntawm impurity tswj rau txoj kev siv tau. Peb kho 12 impurities rau lawv: 5 peptides uas ploj lawm, 2 oxidized impurities, 1 dimer, 2 fatty acid shedding khoom, thiab 2 linker-txog impurities. Txhua tus ntawm lawv muaj purity ntau dua 95%, thiab yog nrog los ntawm MS thiab NMR cov ntaub ntawv. Tus thawj coj ntawm txoj haujlwm tau hais tias, "Cov impurities ntawm tilpeptide yog ob zaug ntau dua li lwm cov peptides, tab sis koj tuaj yeem ua tau tag nrho, thiab cov ntaub ntawv ua tiav, uas txuag peb ntau txoj haujlwm." Tom qab ntawd, qhov kev lees paub ntawm lawv txoj kev tau ua tiav tiav, thiab tam sim no lawv tab tom npaj rau kev tshaj tawm.

Case 2: Lub tuam txhab CRO, impurity profileing
Lawv tau ua tiav txoj haujlwm tshawb fawb zoo ntawm tilpeptide, uas yuav tsum muaj kev tshuaj xyuas dav dav ntawm cov txheej txheem impurities. Lawv tau xa peb cov qauv peptide crude, thiab peb tau ua LC-MS tsom xam, txiav tawm cov qauv ua tau ntawm ob peb yam tsis paub meej, tom qab ntawd muab cov khoom sib xyaw ua ke, thiab muab piv rau lub sijhawm khaws cia thiab huab hwm coj, thiab tau lees paub plaub qhov tsis huv tshiab - ob ntawm lawv tau txuas ntxiv- cuam tshuam, thiab ob ntawm lawv yog cov kua qaub sib txawv. Tus neeg siv khoom siv cov ntaub ntawv no los kho cov impurity profiles thiab ua tiav cov neeg siv khoom lees paub.

Case 3: Stability Study, ib lub tuam txhab biotechnology
Lawv tau tshuaj xyuas qhov ruaj khov ntawm tilpeptide formulation thiab pom tias tus nqi ntawm cov khoom degradation tau nce sai heev hauv cov xwm txheej ceev, tab sis lawv tsis paub tias nws yog dab tsi. Peb tau txheeb xyuas cov qauv los ntawm LC-MS thiab xav tias nws yog qhov tsis zoo ntawm qhov tsis huv ntawm qee qhov chaw Asn, thiab tom qab ntawd muab cov khoom sib xyaw ua ke thiab lees paub nws los ntawm kev sib piv. Lawv tau tsim ib qho kev ntsuam xyuas uas siv cov kev tswj xyuas no thiab xyuas kom meej qhov sib txawv ntawm cov khoom degradation. Tom qab ntawd, thaum lawv xa daim ntawv tshaj tawm, cov ntaub ntawv no yog ib feem ntawm cov kws tshaj lij, thiab vim tias cov ntaub ntawv ruaj khov, tsis muaj nyiaj them poob haujlwm.

Tilpeptide yog ib yam khoom nrov, tab sis kev kawm impurity yog ib txoj hauj lwm me me, tshwj xeeb tshaj yog fatty acid exfoliation khoom thiab linker-txog impurities, uas ntau lub tuam txhab ua tsis tau. Yog tias koj tab tom ua kev tshawb fawb zoo lossis kev txhim kho dav dav ntawm tilpeptide thiab xav tau kev tswj tsis huv, thov hu rau peb. Peb tau ua hauj lwm ntau heev, peb paub tias dab tsi yog qhov nyuaj, thiab peb paub yuav ua li cas kom nws tawm.