'GlCfl THIEU PHl/ONG PHAP P H A N TICH NHl|T TRONG LI/0NG VA O^NG DUNG TRONG CONG TAC KIEM NGHIEM
LE THI THU. NGUYEN THI QUYNH GIANG. VU HA KHUE Vien Kiem nghiem thuoc Trung icffng
1. Khai quat cdc phinmg phap phan tich nliiet Phan tich nhiet bao gom cac phuong phap phan tich dua theo su thay ddi eac tinh chat vat ly va hda hpc cua vat li?u dupe khao sat trong sir thay ddi cuong biic va dinh tnroc ciia nhiet dp. Trong phan tich nhiet eo nhieu phuong phdp cu the: quet nhiet lupng vi sai (Differential Thermal Scanning Calorimetry - DSC), phan tich nhiet vi sai (Differential Thermal Analysis DTA), phan tich nhiet trpng lupng (Thermogravimemetric Analysis - TGA)...
2. Phan tich nhiet trong lirpng TG-TGA 2.1. Binh nghia
- Phan tich nhiet trpng lupng (Thermogravimetry TG hay Thermogravimetric analysis - TGA) la phuong phap theo doi si^ thay ddi khdi lupng theo thdi gian hoac nhiet dp khi mlu dupe dat trong mdt mdi trudng nhit dinh va dupe gia nhiet theo chuong tiinh.
- Phuang phap nay dupe dimg de nghien ciiru su thay ddi cua khdi lupng mau trong qua Irinh gia nhiet nhu qua trinh dehydrat hda, oxy hda - khii, phan hiiy
- Chuong trinh nhiet cd thi bao gdm: dot ndng hoac lam lanh vdi mpt tdc dp nhSt dinh hoac gift nhiet dp mlu la hing sd hoac mdt sd kieu gia nhiet khae phiic tap hon.
Hinh 1. Mot chuong trinh nhiet dcm gian thirang dung - M I U thii (sample): la phan vat chat dupe dat vao trong thiit bi d l bit diu qua trmh gia nhiet va cac san phim phan ung thu dupe trong sudt qua trinh gia nhiet.
- Dd thi thu dupe gpi la dudng cong TGA. Ddi khi d l tang dp phan giai cua cac budc mat khdi lupng tren
dudng TGA, ngudi ta se lay dudng DTG (Derivative Themogravimetric) la dudng dao ham bic nhat cua dudng TGA. DTG khdng phai la phep do vi sai ma chi don thuan la lay dao ham bang cdng cu toan hpc, cd the thue hien dl dang bing phin mim may tinh.
Dudng DTG cdn cho ta biet tdc dp thay ddi khdi lupng ciia mau (dm/dt).
Ouimg cong DTG
Hinh 2. Do thi bieu dien su mat khdi luong do nhiet cua Vinblastin sulfat
2.2, Nguyin ly - ung dung
- Khi mdt chat dupe nung ndng thi tinh chat vat ly va ban chat hda hpc cua nd bi thay ddi. Qua trinh nay dupe bieu diin bang mdt phan ling hda hpc va cac ham nhiet dpng dac trung cho tinh chat ciia he.
- TGA ghi nhan nhirng thay ddi vl khdi lupng cua mau thu vdi tu each mdt ham cua nhiet dp va thdi gian. Mau thii dupe dat trong mdt ndi nung dupe ket ndi vdi mpt can vi sai va nung ndng theo mdt chu trinh nhat dinh hoac dupe giii ding nhiet trong mdt thdi gian nhat dinh. Mdi trudng nung ndng cd the la khi tro (nhu nito) hoac khi phan img (khdng khi hay oxi). Chu trinh nung ndng cd the dupe bit dau trong mdi trudng khi tro rdi sau dd chuyin sang khi thudng tai rapt diem xac dinh de hoan thanh qua trinh phan tich. Nhiing thay ddi ve khdi lupng dupe xac dinh tai nhiing nhiet dp nhat dinh lien quan tdi nhiing thay doi ve thanh phin trong mlu thu nhu dehydrat hda, phan hiiy (decomposition), cae phan ung oxi hda hoac khu, cac phan ung hoac thay ddi khae. Phd hdng ngoai (FTIR) hay phd khdi (MS) cd the dupe su dung ciing vdi TGA de phan tich va xac dinh nhirag pha khi cd mat trong mau thu tai nhiet dp do.
Tap chi K I £ M NGHIEM THUOC - So 1.2014; Tap 12.(43)
- IJTng dung: dugc ling dung d6 do ham luong va tdc do ttiay d6i kh6i luong cua mau, xac dinh ham luong im va bay hoi ciia m5u, phan tich dinh iirong thanh phin khoang vat hoac thanh phin cac chat c6 hoat tinh nhiet trong mlu nghien ciiu, ....
2.3. Thiit hi
c i u tao gom 4 phan chinh:
- Can dien tu v6i do nhay cao voi do phan giai
< 0,001 mg va bp di8u Ichien can;
- Lo gia nhiet (furnace) va sensor nhiet dp;
- Bo phin diSu khi6n nhiet dp;
- Bp phan nhan va xu ly s6 lieu thu duoc tit thiet bi.
Hien nay tren thi tnrong co nhiSu loai can: can diing, can treo va can njm ngang. Theo khuyen cao thi t6t nhit la nta sii dung he thdng can va Id nhiet CO thiat vi nim ngang (Horizontal Balance & Furnace) do CO dp on dinh cao.
t
cap otu^ <£$L Ldgiaoluft -Hinh 3. Sa do mo hinh ciia may TGA 2.4. Cac chu y trong qua trinh phan tKh mau 2.4.1. Hien tuong tang khdi luong do
Khi su dung mau cd the tich ldn se ed mdt anh hudng gay ra bdi nguyen ly Archimedes: "Khi mot v§t thi dupe nhiing chim trong mot chSt long thi chat long se tac dung len vat mpt lire bang ehinh trpng luc cua lupng chat Idng bi chiem ehd, nhung luc nay cd chiiu nguac vdi chieu cua trong lire". Neu the tich cua mau cdng vdi vat giu mau (chen + sensor) la V (lit), ap suat ciia dong khi la P (atm), khoi luong mol phan tii cua khi la M (g), thi d nhiet dp T (dp K) khdi lupng ciia lupng khi bi chiem cho la:
m (g) - MPV/RT (coi khi la ly tudng) (vdi R la hang sd khi cd don vi la l.atm/mol.K) Khi mau dupe gia nhiet, ty trpng ciia khdng khi
xung quanh giam xudng (do gian nd nhiet), trong khi ti trpng cua chat rin gin nhu khdng doi. Vi vSy l^c tac dung len mau giam xudng dan den hien tuong tang khdi lupng ao khi gia nhiet (mSc du trong mh cd the chua cd hieu ling thay ddi khdi lupng nhung may van ghi nhan dupe sir tang khdi lupng ao nay).
Vi du: N I U thi tich mlu + chen nxmg = Icm'
^ 0,001 lit, ap suit ddng khi thdi vio bing 1 atm, khi thdi vao la nito (cd M = 28g), hang s6 khi R = 0,082 l.atm/mol.K thi khdi lupng ao se la 0,8 mg khi nhi8t do tang tir 300K len lOOOK.
Mpt so each di loai trie hien tumtg tang khdi lirang ao:
Cdch I: Tien hanh 2 thi nghiem:
- TN 1: Chay mlu cin phan tich
- TN2: Chay mau trang vdi chit tra nhi?t cd thi tich tuong tu nhu mlu phSn tieh.
- Liy dudng cong TGA d TNI trii di dudng cong TGA d TN2: Do 2 mau cd cung thi tieh thi sir tang khdi lupng ao la tuong ddi gidng nhau.
Cdch 2: Tiin hanh vdi lupng mlu rit it, khi dd sir tang khdi lupng ao la khong dang kl, cd thi bo qua dupe.
Cdch 3: Sis dyng mdt he Id ddi: mpt ben la mlu phan tich, mdt ben la mlu tro nhiet cd ciing thi tich, chiing se dupe gia nhiet ddng thdi, hoan toan gilng nhau. Tuy nhien eich nay lam cho gid thanh cua thi6t bi tang cao.
Khuyin cao:
- Vdi mlu ed hieu img mat khdi lupng ldn nin ti6n hanh theo each 2 vua 6a tdn kem hon each 3 va d5 tdn cdng sire hon each 1, ket qua thu dupe van co dp chinh x^c cao.
- Rieng vdi mau cd hieu ung mat khdi lupng nho, de tang dp phan giai thi phai lam theo each thii nhat.
2 4.2. Cac hieu img mdt khdi luong chong len nhau Tren thue te cd nhung chat cd nhieu hieu ling mat khdi lupng, cd khi la tach nhau hoan toan hoac ehdng len nhau, tire la hi8u ling mit khdi luong M nhat chua xay ra hoan toan thi hi8u ung mit khdi luong thir 2 da xay ra. Do vay di tang dp phSn giai xem cd phai hai hi6u ung mit khdi lupng chong len nhau mpt phin hay khdng ngudi ta lly dao ham bSc 1 ciia dudng cong TGA la dudng DTG, Iiic 66 chiing ta se thiy rd hon cac dinh pic tuong ung vdi mdi hi^u ling mit kh6i lupng trBn dudng TGA.
T^p cbi KIEM NGHIEM THUOC - SS 1.2014; Tap 12.(43)
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- Dinh tinh nhdm cau tnic hda hpc, - Xae dinh mat khdi lupng do lam khd;
- Xae dinh ham lupng cin sau nung.
Cac Dupe dien phd biin nhu USP, BP ciing da cd chuyen luSn chung va mot sd chuyen luan ri8ng qui dinh xac dinh mit khdi lupng do lam khd tien hanh bing phuang phap TGA. Uu diim cua phuong phap la:
L-^i.i.iiJ,'.-irij^-' '""'" 'i";;.""i""i""r"'i";':""i"":i"r:::r^ . sir dung mpt lupng mau rat it;
- Can phan tich vi luong duoc tieh hpp trong may Hinh 4. Do Ihi bieu diensu mal khoi lu^mg do nhiet cua ^^^^ ^^^^ ^ ^ l^g^ ^^ l ^ ^ g ^^^ ^ . ^ ^. ' ^^^^ ^^-^^ ^^
" *• ^ va thdi gian, khdng bi anh hudng eiia mdi trudng ben Tren Hinh 4 la dd thi bieu dien su mat khdi lupng ngoai va thao tac lam ngupi de can gidng nhu phuong do nhi8t cua dong sulfat. Dudng biiu diin phia tren phap say dimg tii say.
la dudng eong TGA cho ta thiy 2 hieu ling mit khdi . Hiin thi tu ddng kit qua (%) giam khdi lupng, lupng rJiung khdng ro rang. Dl biet dupe 2 hieu ling cd biiu dd theo doi dupe cac bude eua qua trinh mit mat khdi lupng nay cd ehdng len nhau hay khdng ta khdi lupng.
quan sat o duong cong phia duoi, 2 dinh pie tuong ^.^-^ ^^ ^^ , ^ ^ ^ ^^.^ p ^ „ ^ ^,.„ g p ung vm 2 lan mat khoi lupng, co the thay rd la hieu ^ g p 34 ^ j ^^^ ^. ,55^ ^^ ^^ ,,„^, ^ , ^ i j , img mat Idioi iupng^ thu nhat xay ra ehua hoan toan ^^„>„ .^ , . ^^ ^ H O ^ „ - ^ 2„(,„ ; , j ^ l^j, th, hien img mat khoi lupng thu hai da xay ra. ^ ^ ^ ^ ^ ^ ^., , ^ g ^ ^ ; p^^^^ , y „g^ig^_ ^^^_^g,..
3. iTng dung cua phuwng phap phan tich nhi^t trong da tien hanh xae dinh (%) mit khdi lupng do lam khd l u ^ g trong cdng tic ki§m nghi€m tren may TGA ciia mot sd mSu cu the. Kit qua thu Phuong phap phSn tich nhiet trpng lupng (TGA) dupe dem so sanh vdi ket qua (%) giam khdi lupng do da dupe eac nude tren thi gidi ling dung tir rat lau say da dupe tien hanh bang phuong phap say thdng trong phan tieh va kiem tra chit luong thudc ciing thudng hoac vdi ham lupng nudc eua mlu thii' dupe nhu nguyen lieu lam thudc. Phuong phap dupe diing xac dinh bang phuong phap Karl Fischer. Dieu kien chu yeu de: tien hanh va ket qua thu dupe nhu sau:
Bdng 1. Chuong trinh gia nhiet dp dung cho timg chat TT
1 2 3 4 5 6 7 8 9 10 11 12 13 i4 15
Mau thu Acid folic Amoxicillin Uihydrat Ampicillin sodium Betamethason valerat Cimetidin Ciprofloxacin. HCI Dexamethason Dexamethason acetat ETythromycin Ethinylestradiol Gentamycin sulfat Lamivudm Nystatin Paracetamol Praziquantel
KL(mg) 4 5 5 3 3 3 14 3 2,5 3 6 3 4 5 3
Chircng trinh gia nhiet Gia nhiet ]0°C /phiit tOr nhiSt do ph6ng tai 230''C Gia nhiet vcri toe dp S^C /phut tir 25 den 120''C, duy tri nhiet do I20°C /120 phiit ho|c din khi ducmg n6n on difth.
Gia nhiet 10 "C /ptiiit tir nhiet do phdng t6i 195''C.
Gia nhiet 10''C /phut tir nhiet do phong toi 2O0''C.
Gia nhiet lO^C/phiit tir nhiet do phong toi ISCC Gia nhiet 5''C /phut tii 20 toi 120 "C, duy tri a 120°C /40 phut.
Gia nhiet 1 O^C/phiit tir nhift do phong toi 160°C.
Gia nhiet ICC/phiittirnhift do phong toi \6Q°C.
Gia nhiet S^C /phut tir nhiet do phong toi 110°C.
Gia nhiet 5''C /phiit tir 20 tdi 1 OS'-C, duy tri a 105°C /120 phiit.
Gia nhiet S^C /phut tir nhiet do phong tai 1 ICC, duy tri 6 11CC /3h.
Gia nhiet 5''C/phut tir nhiet d§ phdng toi 110°C, duy trio UO^Cden khi duong nen on djnh.
Gia nhiet 5''C /phiit tir nhif t do phdng toi 115°C, duy trt 6 11 S^C din khi duong nin on djnh.
Gia nhiet S^C /phiit tiJr 25 den 105''C, duy tri nhiet do I05''C /120 phiit Gia nhiet 5''C /phiit tii 25 din lICC, duy tri nhiet do 11 O^C /120 phiit.
Tai lifu tham khao WHO/PHARM/89,544 EDM/QSM/2008,2 WHO/PHARM/89.544 WHO/PHARM/91.555 WHO/PHARM/91.555 WHO/PHARM/97.595 WHO/PHARM/89.544 WHO/PHARM/89.544 WHO/PHARM/92 558 EDM/QSM/2002.8 EDM/QSM/2006.I EDM/QSM/2006.1 WHO/PHARM/92.558 EDM/QSM/2008.2 WHO/PHARM/95.577
Tjp chi KIEM NGHIEM THU6C - So 1.2014; T8p 12.(43)
- iTng dung: duoc iing dung dl do ham lupng va tdc dp thay ddi khdi lupng ciia mlu, xac dinh ham lupng Im va bay hoi cua mau, phan tich dinh lupng thanh phan khoang vat hoac thanh phan cac chat cd hoat tinh nhiet trong mlu nghien ciiu,....
2.3. Thiit bi
Cau tao gdm 4 phan ehinh:
- Can dien hi vdi dp nhay cao vdi dp phan giai
< 0,001 mg va bd dieu khien cSn;
- Ld gia nhi$t (fiunace) va sensor nhiet dd;
- Bp phan dieu khien nhiet dp;
- Bd phan nhan va xu ly sd lieu thu dupe tii thiet bi.
Hien nay tr8n thi trudng cd nhieu loai can: can dimg, can treo va can nam ngang, Theo khuyin cao thi tdt nhat la nen su dung h? thdng can va Id nhiet ed thiit kl nim ngang (Horizontal Balance & Furnace) do ed do dn dinh cao.
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Hinh 3. Sado mo hinh cua may TGA 2.4. Cac chuy trong qua trinh phan tich mdu 2.4.1. Hien tu0igtdngMioiluongdo
Khi su dung mau cd the tich ldn se cd mpt anh hudng gay ra bdi nguyen ly Archimedes: "Khi mpt vat the dupe nhiing chim trong mdt chat Idng thi chat Idng se tac dung len vat mdt luc bing chinh trpng lire cua lupng chat Idng bi chiem chd, nhung lire nay cd chieu ngupe vdi chieu cua trpng lire". Neu the tich ciia mau cdng vdi vat giu mau (chen + sensor) la V (lit), ap suat cua ddng khi la P (atm), khdi lupng mol phan tir ciia khi la M (g), thi 6 nhiet dp T (dp K) khdi lupng cua lupng khi bi chiem cho la:
m (g) = MPV/RT (coi khi la ly tudng) (vdi R la hang sd khi cd don vi la l.atm/mol.K) Khi mlu dupe gia nhiet, ty trpng cua khdng khi
xung quanh giam xudng (do gian nd nhiet), trong khi ti trpng ciia chat ran gin nhu khdng ddi. Vi vay luc tic dung ISn mau giam xudng din den hi?n tupng tang khdi lupng ao khi gia nhiet (mac dii trong mlu cd thi chua cd hieu umg thay doi khdi lupng nhimg may vin ghi nhan dupe sir tang khdi lupng ao nay).
Vi du: N I U the tich mlu + chen nung = Icm^
= 0,001 lit, ap suat ddng khi thdi vao bing I atm, khi thdi vao la nito (cd M = 28g), hing sd khi R = 0,082 l.atm/mol.K thi khdi lupng ao sg 1^ 0,8 mg khi nhi6t do tang tu 300K I8n lOOOK.
Mot sd cdch di lo^i trir hien twang tdng khSi luong do:
Cdch } . Tien hanh 2 thi nghiem:
- TNI: Chay mlu cin phan tich
- TN2: Chay mlu trang vdi chit tro nhi8t co thi tich tuong tu nhu mau phan tich.
- Lly dudng eong TGA d TNI trii di dudng cong TGA d TN2: Do 2 mau cd eimg thi tieh thi su tang khdi lupng ao la tuong ddi gidng nhau.
Cdch 2: Tien hanh vdi lupng mlu rit It, khi dd sit tang khdi lupng ao la khdng dang kl, ed thi bd qua dupe.
Cdch 3: Su dung mdt he Id ddi: mdt ben la n^u phan tich, mpt b8n la mlu tro nhiSt ed ciing the tich, chiing se dupe gia nhiet ddng thdi, hoan toan gidng nhau. Tuy nhien each nay lam cho gia thanh ciia thiit bi tang cao.
Khuyen cdo:
- Vdi mlu cd hieu umg mat khdi lupng ldn nen tiin hanh theo each 2 vura d& tdn kem hem cich 3 va do tdn cong siic hon each 1, kit qua thu dupe vin cd dg chinh xac cao.
- Rieng vdi mau cd hieu ung mit khdi lupng nho, de tang dp phan giai thi phai lam theo each thii nhat.
2.4.2. Cac hieu img mdt khoi luong chong len nhau Tren thuc te ed nhiing chat co nhieu hieu ling mSt khdi lupng, cd khi la tach nhau hoan toan hoac ehdng len nhau, tuc la hieu ling mat khdi lupng thii nhat chua xay ra hoan toan thi hieu ung mit khdi lupng thii 2 da xay ra. Do vay d l tang dd phan giai xem cd phai hai hieu ling mit khdi lupng ehdng len nhau mpt phan hay khdng ngudi ta lay dao him bac 1 ciia dudng cong TGA la dudng DTG, liie dd chiing ta se thay rd hon cac dinh pie tuong ling vdi mdi hieu ung mit khdi lupng h-en dudng TGA.
Tap chi IGEM NGHIEM THUOC - S6 1.2014; Tap 12.(43)
- -' r-r - Djnh tinh nhdm eau tnic hda hpc;
„__ - Xac dinh mit khdi lupng do lam khd;
_ - Xac dinh ham lupng can sau nung.
•^^ r^-^-^ .1^ Cac Dupe diin phd biin nhu USP, BP cung di cd '""""•""•""•""'"'•""•' chuy8n luan chung va mot sd chuyen luan rieng qui
~ \ ^ dinh xic dinh mit khdi lupng do lam khd tiin hanh bang phuang phap TGA. Uu diim ciia phuong phap la:
-°"""'.'.X-' •" ' - ' ^ - Sii dung mpt lupng mau rat it;
r,- • ^ ^ - > , . , . . - , - . - , , / , , • Can phan tich vi luong duoc tich hop trong miy Hmh 4. Do thi bieu dien su mat khoi luone do nhiet cua x. i, • •> i-- .^ i - -^ j - ^i ! • - . * -_ ^ * • cho p h e p can lien tuc l u p n g m a u m a t di theo nhiet dp
•*• ^ v a thdi gian, k h o n g bi i n h h u d n g ciia mdi t r u d n g ben Tren H i n h 4 la dd thi bieu dien sir m a t khdi l u p n g ngoai v a t h a o tac lam ngupi d e c i n giong n h u p h u o n g do nhiet cua d d n g sulfat. D u d n g bieu d i i n phia tren p h a p say d u n g hi say.
la dudng eong TGA cho ta thiy 2 hieu ung mit khdi . Hiin thi tu dpng kit qua (%) giam khdi luong, lupng nhung khdng rd rang. De biet duoc 2 hieu ling cd biiu dd theo ddi dupe cac budc ciia qua trinh mit mat khdi lupng nay ed chong len nhau hay khdng ta kii^j lupng.
quan sit d dudng cong phia dudi, 2 dinh pic tuong T - u, 11.- T-. >-- r.n o^^.^
7 .- -. ,1 f , , ;. , , , J , A ^ ,. , . . Tren co so tham khao Duoc dien BP. 2010, ung vol 2 lan mat khoi luong, eo the thay ro la hieu TTC-D -^A - • ^'- i - u- - i. ^3- *i--. i-
, i. , . ^ - , .1 . ; ; - , , , ; USP. 34 va cae tai lieu bao cao hoat dong thiet lap ung mat khoi luong thu nhat xay ra chua hoan toin , ; x ..; . ii.tr/-* ^' - -./.^/^'.*'! I'i.
, , , . . , X , , ; . , . , , . . . , chuan quoc te cua WHO tu nam 2000 den nay, ket thi hieu ung mat khoi luong thu hai daxay ra. i .r^i u- -^.i,- * - u- .i.- L - L- .-•
, ^ hpp voi khao sat them tai phong thi nghiem, chung toi 3. iTng dung cua phmm^ phap ph§n tich nhiet trpng da tiin hanh xac dinh (%) mit khdi lupng do lam khd lupng trong cdng tic kiem nghif m tr8n miy TGA cua mpt sd mlu cu tlil. Kit qua thu Phuong phip phan tich nhiet trpng lupng (TGA) dupe dem so sinh vdi ket qua (%) giam khdi lupng do da dupe cac nude tren thi gidi ling dung tu rit lau say da dupe tien hanh bing phuong phap sly thdng trong phan tich va kiem tra chit lupng thudc cung thudng hoac vdi ham lupng nudc ciia mlu thij dupe nhu nguyen lieu lam thude. Phuong phip dupe diing xac dinh bang phuong phap Karl Fischer. Diiu kien chii yiu de: tien hanh va ket qua thu dupe nhu sau:
Bdng 1. Chuong trinh gia nhiet dp dung cho timg chat TT
1 2 3 4 5 6 7 8 9 10 11 12 13 14 '5
Mau thir Acid fohc Amoxicillin trihydrat Ampicillin sodium Betamethason valerat Cimetidin Ciprofloxacin HCI Dexamethason Dexamethason acetat Erythromycin Ethinylestradiol Gentamycin sulfat Lamivudin
•Nystatin Paracetamol Praziquantel
KL(mg) 4 5 5 3 3 3 14 3 2,5
3 6 3 4 5 3
Chtr&ng trinh gia nhiet Gia nhi^t 10''C /phiit tii nhiet do phong toi 230''C Gia nhiet voi toe do 5''C /phiit tir 25 d^n 120''C, duy tri nhiet do 120''C /120 phiit hoac den khi duong nen on diflh.
Gia nhiet 10 "C /phiit tir nhi?l do phong toi !95''C, Gia nhi^t ICC /phiit tir nhiet do phong toi 200''C.
Gia nhiet ICC /phiit tii nhiet do phong toi U C C . Gia nhiet 5''C /phtit tir 20 tai 120 "C, duy tri 6 120°C /40 phiit.
Gia nhiet 1 O^C /phiit tCr nhi?t do phong toi 160''C.
Gia nhi?t ICC /phiit tir nhiet do phong toi leo^C Gia nhiet 5''C /phiit tir nhiet do phong lai 110''C.
Gia nhi?t 5°C/phiit tir 20 to! I05°C, duy tri a 105''C /120 phiit.
Gia nhiet 5°C /phiit tir nhiet do phong toi 110''C. duy tri 6 11CC /3h.
Gia nhiet 5''C /phiit tu nhiet do phong toi 11CC, duy tri 6 110''C den
•chi dircmg nen on dinh.
Gia nhiet S^C /phiil tir nhiet dO phong toi 115°C, duy tri d 115''C din dil duong nen on dinh.
Gia nhiet 5''C/phiit tii 25 den !05''C,duy trinhieldp lOS^C/120 phiit.
Gia nhiet S^C/phiit tir 25 den 11 O^C, duy tri nhiet d6 llO^C/UO phiit.
Tai lieu tham khao WHO/PHARM/89.544 EDM/QSM/2008 2 WHO/PHARM/89.544 WHO/PHARM/91.555 WHO/PHARM/91.555 WHO/PHARM/97.595 WHO/PHARM/89.544 WHO/PHARM/89.544 WHO/PHARM/92.558 EDM/QSM/2002 8 EDM/QSM/2006.1 EDM/QSM/2006.1 WHO/PHARM/92.558 EDM/QSM/2008.2 WHO/PHARM/95.577
T a p chi K I E M N G H I E M T H U O C - S« 1.2014; T J p 12.(43)
16 17 18 19 20
Prednison Streptomycin sulfat Telracychn. HCI Vinblastin sulfat Vincristin sulfat
5 5 10 10 10
Gia nhiet S^C/phut tii nhiet do phong toi lOS^C, duy tri 6 105''Cden khi duone nen on dinh.
Gia nhiet 5''C /phiit tii 20 toi 1 OS^C, duy trt cr ]05''C/240 phut.
Gia nhiet 5''C /phiit tur nhiet do phong toi 105''C, duy tri a 105'<: d^n khi duong nen on dinh.
Gia nhiet 5''C /phiit tu nhiet do phong toi 200''C Gia nhiet 5^0 /phiit tir nhiet do phong toi 200"C.
EDM/QSM/2009.2 WHO/PHARM/97.595 EDM/QSM/2006.1 USR 34 USR 34 Tat ea cac thuc nghiem tren deu dupe tien hanh tren thiet bi TGA/DSC I eua hing Mettler Toledo hong diiu kien thdi ddng khi nito tinh khilt 99,999% vdi tdc dp 40 ml/phiit, chen mlu nhdm oxyd.
Bdng 2. Ket qua (%) mdt khoi lucmg
TT 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 IS 19 20
Mau thu Acid fohg Amoxicillin trihydrat Ampicillin sodium Betamethason valerat Cimetidin Ciprofloxacin HCI Dexamethason Dexamethason acetat erythromycin Ethinylestradiol Gentamycin sulfat Lamivudin Nystatin Paracetamol Praziquantel Prednison Streptomycin sulfat Tetracyclin HCI Vinblastin sulfat Vincristin sulfat
Sd Id/SKS 0199004 0706017 106133 0103125 0411046.02 0212290.02 0197025 0200014 029573 0107164 0612011,02 0312146,03 0195022 0208019 0103166 0107235 0298003 0411002.02
Lot 1 Lotl
(%) malKL bangpp TGA 1
8,21 13,15 1,11 0,55 0,02 1,66 0,05 0,19 2,24 1,70 10,74 0,03 4,24 0,0 0,01 0,11 7,92 0,94 11,93 8,52
2 8,24 13,17
1,05 0,63 0,07 1,91 0,06 0,18 2,08 1,67 10,89 0,02 4,22 0,0 0,02 0,12 7,46 0,78 12,12 8,61
3 8,04 13,12
1,11 0,25 0,03 1,81 0,07 0,16 1,94 1,76 10,81 0,05 4,19 0,0 0,01 0,10 7,98 0,86 12,51 8,50
Trung binh 8,14 13,14
1,09 0,48 0,04 1,79 0,06 0,18 2,09 1,71 10,81 0,03 4,22 0,0 0.01 0,11 7,79 0,86 12,19 8,54
(%) mat KL bhngpp kkdc LOD
0,14 0,04 0,13 0,1 0,89 0,04 3,14 0,06 0,0 0,15 5,10 0,39
KF 8,0 13,45
1,13
6,02
2,18 12,71
Yeuc5u< 15%
Yeu cau < 12%
Nhdn xet: Ket qua cho thay (%) mat khdi lupng do bang phuong phap TGA gan nhu giong vdi cac kit qua (%) mat khdi lupng do sly khd su dung tii sly.
Rieng ddi vdi cac mau cd ham am dupe xac dinh bing phuong phap KF thi cdn phai ke den ham lupng dung mdi tdn du thi mdi cd the ket luan dupe chinh xac, tuy nhien vdi nhiing khao sat ban diu, kit qua thu dupe rtr 2 phuang phap nay la tuong ddi phu hpp vdi nhau.
4. Kit luan
Tren day la nhiing khii niem co ban vl phuong
phap phan tich nhiet tt-png lupng (TGA) va mot sd thuc nghiem ban dau ling dung phuong phip trong kiim nghiem. Tuy ring mdt sd Dupe dien di cd chuyen lujin ehung nhung sd lupng chuyen luan rieng quy dinh ap dung phuong phip TGA edn rit it, do vay viec khao sat sir phu hop eiia phuong phap ap dung tren cac mlu cu the can dupe tien hinh. Hien nay chiing tdi vin tiep tuc khao sit de ip dung phuang phap tren cac mlu hiSn cd tai phdng thu nghiem va su dung kit qui nay dl ddi chieu va chiing minh cho dp tinh khilt ciia hoat chat hong viec thiet lap chit chuin.
Tai lieu tham khao 1. A beginner's guide for thermogravimetric analysis - Perkin Elmer.
2. Collaborating Centre for Chemical Reference Substances - WHO, from 1995 to 2009.
3. Gidi thieu ve cac phuong phap phan tich nhiet va phuong phap phan tich nhiet trong luong (TGA) cua Mettler Toledo, 4. Thermal Analyzer - Shimadzu Asia pacific Pte Ltd Singapore.
5. The BristishPharaiacopoeia 2010.
6. The United State Pharmacopoeia 34.
Tap chi KIEM NGHIEM THU6C - Sl 1.2014; TSp 12.(43)
