by Reversed-Phase High- Performance Liquid Chromatography", Joumal of Chromatographic Science, Volume 27,

Issue 9, p. 5 6 1 - 5 6 5 .
5. European Medicines Agency, Committee for Medicinal Products for H u m a n U s e (2009), Guideline on Validation of
Bioanalytical Methods
6. U.S Department of Health and Human"Services, Food and D m g Administration, Center for D r u g Evaluation and
Reseach (2003): Guidance for Industry - Bioanalytical Method Validation.
• Yan Zhang, Hai-Long Wu, A - L m Xia (2007), "Fluorescence determination of metoprolol in h u m a n plasma b y Uilinear
decomposition-based calibration techniques". Anal. Bioanal. Chem , Vol. 3 8 6 , p. 1 7 4 1 - 1 7 4 8 .

SUMMARY
A simple, specific and sensitive HPLC method has been developed for the determination of metoprolol in human
plasma. Separation of metoprolol and methylparaben (internal standard) was achieved on a CIS column (5 pm, 250^4,
mm i.d) using fluorescence detection with X^^ 229 nm and X^^=309 nm. The mobile phase consists of acetonitrile and
phosphate buffer pH 35 with suitable ratio. The analysis was performed in less than 10 minutes with a flow rate of
1.5 ml/min The assay was linear over the concentration range of 2.0-100 ng/ml. The LLOQ was 2.0 ng/ml. The extraction
recoveries were found to be 98.1% to 99 6%. The intra- and inter-day precision and accuracy were within 90% • 115%.
This method can be used for BE studies of metoprolol preparations.

NGHIEN CtfU TINH CHE NGUYEN LIEU

VINBLASTIN SULFAT VAVINCRISTIN SULFAT LAM CHAT DOI CHIEU
NGUYEN TUONG VY TRAN BACH DUONG MAI THANH HA. LE THI THU
Trudng Dgi hgc Dugc Hd Npi Vien Hoa hgc Cong nghiep Viet Nam Viin Kiem nghiem thuoc TW

1. Dat van de
Hien nay, ung thu la mdt tiong nhiing can benh gay tu vong cao nhat the gidi. Trong phac dd dieu trj mOt so
loai ung thu d cac benh vien ung budu hien nay ed mat hai hoat chat Vinblastin sulfat (VBL) vd Vincristm sulfat
(VCR).
Them vao do, Dugc dien Viet Nam IV vd cae Duac dien nude ngoai (Dugc dien Anh, My, Chdu Au, Qudc te,,
Trung Qudc) da cd chuyen luan ve Vinblastin sulfat va Vincristin sulfat, deu dp dung ede phuang phap phan tich
sir diing cac thiet bj hien dai yeu cau phai co chdt ddi chieu Vinblastin sulfat va Vincristin sulfat.
Vi vay, de chu ddng cho viec Idem tra chat lugng che pham Vinblastin sulfat va Vincristin sulfat phdi cd chat
ddi chieu. Theo quy djnh, nguyen lieu diing de thiet lap chdt ddi ehieu phai la nguyen lieu tinh khiet. Thong
thudng sau khi phdn lap, do tinh khiet ciia hoat chat chi thudng dat khodng 80% den 90%. Qud trinh tinh che tiSp
theo nham loai tiep cac tap de lam tang do tinh khiet ciia boat chat. Xudt phdt tir ly do tien, ehiing tdi tien hanh
tinh che hai nguyen lieu Vinblastin sulfat va Vincristin sulfat de thiet lap ehdt ddi chieu phuc vu edng tdc kiem tra
va gidm sdt ehdt lugng thudc tien thi truong.

CH3 ^Of^\ .CH HO jf-0 OH,

0 c O CHj
Hmh la Cdng thuc cdu tgo cua VBL Hinh lb- Cdng thuc cdu tgo cua VCR

Tap chi KIEM NGHIEM THUOC - So 1.2013; Tap l l . ( ^

2. T h ^ nghidm 2.2.2.1. Phuong phdp tinh ehe
2.1. Thiet bi,d^ngc^, hda chdt, chdt chudn Do VBL vd VCR cd can true hda bgc tuong tu nhau
2.1.1. Thietbi, dt^ingcg nen tmh chit hda hgc gidng nhau. Vi vdy, qua trinh tinh
Cae thiet bj, dung cp cua Vien Kidm nghiem thudc cbl tidn hdnh gidng nhau.
Trung ucmg (da dugc hi?u chudn theo ISO/IEC 17025 VBL vd VCR tan tdt tiong nude vd alcol, do vay
va GLP) vd Vi?n Hda hgc Cdng nghiep Viet Nam g6m: su dvmg phucmg phap sac ky phdn bd pha ddo vdi pha
- Mdy sdc ky long cao dp ban dieu chd - Labomatic tmh C18 de tinh che VLB vd VCR thu dugc san phdm
HD3000. tinh khiet cd bam lugng tren 99%. Kiem tia sdn phdm
tinh chd dugc bdng phuang phdp HPLC,
- Mdy sdc ky Idng hieu nang eao - Agilent 1100
(detector DAD) 2.2.2.2. Xdc dinh cau tnic, nhan dang chdt
- May phdn tieh nhiet tigng lugng - TGA Mettler Tir chat tinh khiet da tinh che dugc, xac djnh cdu
Toledo. tnic bdng cde phuang phdp hien dai nhu IR, NMR, LC-
- Mdy do quang UV-VIS - Hitachi U-3900H. MS, UV-VIS.
- May do phd IR 670-FTIR NICOLET NEXUS. 2.2.2.3. Ddnh gid nguydn lieu trude va sau khi tinh chd
- May cgng hudng tii hat nhdn Bniker Avanee - Mat khoi lugng do 1dm khd (phuang phap phdn
AM500 FT-NMR. tich nhiet tigng lugng).
- Mdy sic ky Idng khdi phd ESI-MS THERMO- - Tap chat lien quan (HPLC).
FINNIGAN LCQ ADVANTAGE MAX. - Dinh lugng (HPLC): so sanh vdi chuan.
- Cgt C18 60 X 500 mm, pha tinh LiehioPrep C18 3. Ket qua va ban loan
edhat 15-25 pm.
3.1. Tinh chi
- Cgt C18 Gemini, 150 x 4,6 mm, 5 pm.
- Cgt C8 Luna, 250 x 4,6 mm, 5 pm. 3.1.1. Ttnh chi VBL (VCR) bdng thiet U sac liy long bdn
- Can phan tich Mettler toledo MS 105, do chinh dieu che Labomatic HD 3000
xdc 0,01 mg. - Cgt sac ky pha dao C18 LiehroPrep 60 x 500 mm,
- May do pH - Metrohm 691 pH meter. cdh^t 15-25 pm.
- Man: VBL (VCR) hda tan tiong hdn hgp methanol
- Cdc dung cu thiiy tinh can thidt cho qud trinh thvre
-nude (1:1).
nghi?m.
- Phdt bien: Detector UV 262 nm (VBL), 297 nm
2.1.2. Hoa chdt, chdt chudn (VCR).
- Chit chuin Vmblastin sulfat JCRS (Nhdt Ban), - Pha dgng: Pha dgng A: Methanol
Lot. VB9501, ham lugng 100% tmh tiieo chit khan, Pha ddng B: Nude
do am 11,4%. Acid sulfiiric 0,05%: 10% hdn hgp pha ddng
- Chdt chudn Vincristin sulfat ICRS (Qudc te), Lot. Chay gradient;
193181, ham lugng 100% x 9,3 mg/lg.
Thdi gian (gi&) Pha d^ngA (%) Pha dpng B (%)
- Acetonitril, Methanol dung cho HPLC.
0 10 90
- Acid sulfuric, Ethanol khan, Diethylamin loai tinh
2 65 35
khiet phdn tich.
6 65 35
ZZ Doi tirffng vd phuang ph^ nghien cuu
8 90 10
2.2.1. Boi tugng nghien dm
- Tdc do ddng: 45 ml/phiit.
Nguyen li^u Vmblastin sulfat va ^%cristin sulfat
ed hdm lugng tien 95,0% tu dd tdi '*Nghien ciiu quy Kit qud: VBL dugc nia giai ra tuang iing vdi thdi
trinh bdn tdng hgp Vinblastin sulfat va Vincristin sulfat gian lim ~ 4 gid vd VCR tuang img vdi thdi gian luu
tu Vindolin va Catharanthin lam thudc chdng ung thu - 7,5 gid.
mdu" thugc "Chucmg trinh nghien ciiu khoa hgc cdng 3.1.2. Kit tinh
ngh$ trgng diem qudc gia phdt trien cdng nghiep hda Phdn doan sac ky chiia VBL (VCR) dugc ggp lai,
dugc ddn nam 2020". cd kigt dung mdi, siy dudi dp suat giam <150 mbar d
2.2.2. Phuangphdp nghien ciru nhi?t dg 40 - 50°C vd thu dugc sdn pham d?ng cao.

T»p chi KrilM NGHI$M THUOC - S6 1.2013; Tap 11.(39)

Hda tan sdn phdm tiong ethanol khan, aeid boa ddn
pH 4 bdng dung dieh aeid sulfuric 1% trong ethanol
(lie nhe bmh dimg dung djch trong qua trinh acid hoa).
D6 ling tiong 24 gid d nhiet do phdng. Lgc hut chan
khdng dd tiiu ket hia. Hda kdt tua tan hodn toan tiong
ethanol, bd sung tiep ethanol khan, lie nhe. De yen hon
hgp 3 gid 6 nhiet do phdng. Sau do ddng khd d nhiet
do - 80°C, dp suit chdn khdng 2 - 6 mbar trong 48 gicf
va thu dugc sdn phdm tinh ehd d?mg bgt ket tinh mau
trdng.
Hieu suit eiia qua trinh tinh ehd VBL la 70% vd
VCR id 65%.
Hinh 2a. Pho UV-VIS cua VBL chudn
3.2.1.2. Ph6 hong ngoai (IR)
Phd IR cua nguyen lidu Vinblastm sulfat timg vdi phd IR euaVmblastm sulfat chuin JCRS (Nh^t Ban) Lot.
VB9501, dong tiidi cho cde sd sdng ddc tiung d 1773,1616,1458,1231,1117 va 618 c m ' .
^iTi.-
\ 111" '.
Hinh 3iLPh6lRciia VBL chuin
3.2.1.3. Pho NMR
Nguyen li?u sau khi tinh chi dugc xac dinli cSu true
bing ph6 cpng hucmg tit hjt nhan. Ket qua ph6 c6ng
huong tir nhu sau:
'H-NMR (500 MHz; TMSO-d^, i (ppm): 3,57 J (1
H; H-2); 5,14 s (1 H; H-4); 5,13 d (1 H; H-6); 5,80
dil (1 H; H-7); 2,7 - 2,8 m (overlap) (Ha-8); 3,43 m
Tap chi KIEM NGHIEM THUbC - So 1.2013; T«p 11.(39)
3.2. Xdc Sink cdu true, nh^ dgng sdn phdm sou khi
tinh chi
3.2.1. Vinblastin sulfat
- Tinh ehit: Bgt kdt tinh mdu tring.
3.2.1.1. Phd UV-VIS
Song song tidn lidnh do dung dich chuan \%iblastin
sulfat JCRS (Nhdt bdn) Lot.VB9501 va dimg dieh thii
vdi ndng dg 20 pg/ml methanol d ciing dieu kida K€t
qua eho thiy dung djch thu eho dinh hdp thu cue d^i d
bude sdng 215 nm va 266 nm, trimg vdi cdc dinh hdp
thu cvrc d^ii cua dung djch Vinblastin sulfat chuan.
Hinh 2b. Phd UV- VIS cua nguyen li^u VBL
Hinh 3b. Pho IR cHa nguyen U4u VBL
(HP-8); 2,49 - 2,52 m (overlap) (Ha-10); 3,19 - 3,21
m (overlap) (HP-10); 1,69 - 1,74 m (Ho-11); 2,04 m
(HP-U); 6,54 brs (1 H; H-14); 6,39 brs (1 H; H-17);
2,60 - 2,74 m (overlap) (1 H; H-19); 1,35 - 1,40 m
(overlap) (Ha-20); 1,45 - 1,55 m (overlap) (Hp-20);
0,67 ((3 H; 8 Hz; H-21); 2,67 brs (3 H; H-22); 3,07
brs (2 H; H-2'); 1,35 - 1,40 m (overlap) (Ha-4'); 1,45
- 1,55 m (overlap) (HP-4'); 1,15 m (1 H; H-5'); 2,20
m (Ha-6'); 3,84 m (HP-6'); 9,70 brs (1 H; H-9'); 7,32
i/(l H; 8 Hz; H-11'); 7,07 ((1 H; y = 7,5 Hz; H-12');
7,0O((lH;J = 7,5Hz;H-13');7,51(/(lH;y=8Hz;
H-14'); 1,35 - 1,40 m (overlap) (Ha-17'); 1,45 - 1,55
m (overlap) (HP-17'); 3,4 - 3,5 m (overlap) (Ha-18');
3,7 - 3,8 m (overlap) (Hp-18'); 2,45 - 2,50 m (overlap)
(Ho-19'); 3,18 - 3,21 m (overlap)(HP-19'); 1,35 - !,44
m (overlap) (2 H; H-20'); 0,86 ((3 H; / = 7 Hz; H-21');
1,98 brs (3 H; H-25); 3,65 brs (3 H; H-26); 3,78 s (3 H;
H-27); 3,60 brs (3 H; H-28)
"C-NMR (125 MHz; DMSO-rf,; d (ppm): 81,83
d (C-2); 79,32 j(C-3); 75,74 d (CA); 42,07s (C-5);
130,44 d (C-6); 123,47 d (C-7); 49,56 t (C-8); 48,70
((C-10); 44,29 ((C-11); 52,75 s (C-12); 122,50 s (C-
13); 123,47 d (C-14); 119,76 s (C-15); 157,47 s (C-
16); 94,08 d (C-17); 152,42 s (C-18); 63,60 d (C-19);
30,67 ((C-20); 7,60 q (C-21); 37,79 q (C-22); 60,50 (
»n , V nt^.^c • T^r , -
Hinh 4a. Pho MS cua VBL chuan
Kit luqn: Tu phan tich tinh chat va dix lieu ph6 UV-VIS, IR, NMR va MS ket hgp so sanh voi tai lieu tham
khao CO the khSng dinh dugc chit sau khi tinh che la Vmblastin sulfat.
3.2.2. Vincristin sulfat
- Tmh chSt: BOt k8t tinh mau tt&ig
3.2.2.1. Ph6 UV-VIS
TiSnhanh song song cimg dung dich ehuan Vincristin sulfat ICRS (Quoc t8) Lot. 193181 va dung dich thii cr
nong do 20 ^ig/ml methanol a cimg diSu ki^n.
Hinh 50. Pho UV-VIS ciia VCR chuan
Tan chi KlfiM NGHI$M THU6c - S6 1.2013; T|p 11.(39)
(C-2'); 66,69 J (C-3'); 30,67 ((C-4'); 26,31 rf(C-5');
35,33 f (C-6'); 54,79 s {C-7'); 131,28 s (C-8'); 135,57
s(C-lO'); 111,71 <;(C-11'); 121,66 d (C-12'); 118,49
rf(C-13'); 117,60 <i(C-14'); 128,14 s (C-15'); 112,70
s (C-16'); 30,67 ( (C-17'); 55,91 ( (C-18'); 48,70 (
(C-19'); 33,88 ((C-20'); 6,68 q (C-21'); 173,85 s (C-
22'); 169,85 s (C-23); 170,91 s (C-24); 20,74 q (C-25);
51,49 J (C-26); 55,91 q (C-27); 52,07 q (C-28).
Qua ket qua phan tich ph6 NMR, cac so li$u ph6
chi tiet da dugc xay dimg, dua ra la chinh xac va hoan
toanphuhgpvoicau true ciia phan tir Vmblastin sulfat,
3.2.1.4. Ph6 kh6i lugng (MS)
K6t qua xac djnh ph6 kh6i cua nguySn lieu
Vinblastin sulfat cho pic manh ion phan hi m/z 811,50
phu hgp voi manh ion phan tii m/z cua Vinblastin
chuan la 811,50. Nhu vay phan tu lugng ciia Vinblastin
sulfat la 811,50 phu hgp vdi khoi lugng phan tii eua
Vinblastin sulfat c6 cong thiic phan tii C^^HggN^O^
Hiuh 4b. PfiS MS CUU nguveft li^u VBL
"^
Hmh 54. Pho UV-VIS ciia nguyin lieu VCR
 Kdt qud cho thiy dung dich tiiir cho dinh hip thu eirc dai a buac song 220 nm, 256 nm vd 297 nm, tiling vdi
cac dinh hip tiiu circ dai ciia dung dich Vmcristin sulfat ehudn.
3.2.2.2. Phd IR
Phd IR ciia nguyen lieu Vincristin sulfat trimg vdi pho IR eua chat chuan Vincristin sulfat, ddng thdi cho cdc
sd sdng dac tiimg 6 1749,1670,1458,1229,1117,618 cm''

1 !4i- mi
1 I
i ;,
s
i'-
i
4
Hmh6a.PhdIRc Hmh 6b. Pho IR cua nguyen lieu VCR
3.2.2.3. Pho NMR
Nguyen lieu sau khi tmh ch8 duge xae dinh cau Uiic biing pho cgng hugng hi hat nhSn. Ket qua pho cgng
hudng tit h?it nhan nhu sau:
'H-NMR (500 MHz; DMSO-rf^; S (ppm): 4,44 6ra(H-2); 5,01 - 5,05 m (overlap)(H-4); 5,36 rf (10 Hz; H-6);
5,84(/(/(5Hz; 10Hz; H-7); 2,86rf(15 Hz;H-8a); 3,34m (overlap) (H-8b); 2,57 m (H- 10a); 3,23 m (H-lOb); 1,72
m (H-lla); 1,98 m (overlap) (H-llb); 6,91 brs (H-14); 7,37 brs (H-17); 3,12 m (overlap) (H-19); 1,38 - 1,44 m
(overlap) (H-20); 0,68 (( 7,5 Hz; H-21); 9,03 brs (H-22); 3,07 m (overlap) (H-2'); 2,67 dd (5Hz; 15 Hz; H-4'a);
3,74 rf (15 Hz; H-4'b); 1,06 m (overlap) (H-5'); 2,24 m (overlap) (H-6'a); 3,90 m (overlap) (H-6'b); 9,98 brs (H-
9N); 7,37 rf (7,5 Hz; H-11'); 7,08 t (7.5 Hz; H-12'); 7,01 / (7.5 Hz; H-13'); 7,53 rf (7.5 Hz; H-14'); 1,38 - 1,47 m
(H-17'); 3,50 - 3,64 m (H-18'); 2,85 rf(15 Hz; H-19'a); 3,32 - 3,38 m (15 Hz; H-19'b); 1,41 m (overlap) (H-20');
0,86 ((7,5 Hz; H-2r); 1,94 brs {H-25); 3,47 brs {H-26); 3,86 brs (H-27); 3,64 brs {H-28).
"C-NMR (125 MHz; DMSO-rfp d (ppm): 71,05 rf {C-2); 79,08 s{C-3); 76,79 rf (C-4); 41,77 s (C-5); 130,26
rf (C-6); 123,82 rf (C-7); 49,26 t (C-8); 48,09 (C-9); 41,12 t (C-11); 55,14 s (C-12); 123,99 s (C-13); 124,85 rf
(C-14); 128,28 s (C-15); 157,21 s (C-16); 95,96 rf (C-17); 141,36 s (C-18); 62,60 rf (C-19); 30,74 ((C-20); 7,49
?{C-21); 161,29 rf (C-22); 60,51 ({C-2'); 66,62 s {C-3'); 44,48 ((C-4'); 26,25 rf (C-5'); 35,14 ((C-6'); 52,14 s
(C-7'); 130,40s(C-8'); 135,91 s(C-10');112,07rf(C-ir); 121,68 rf(C-12'); 118,51 rf(C-13');117,64rf(C-14');
128,28 s (C-15'); 113,06 s (C-16'); 30,74 ((C-17'); 55,94 I {C-18'); 49,261 (C-19'); 33,87 t (C-20'); 6,69 q (C-
21'); 173,33 s {C-22'); 169,87 s {C-23); 169,42 s (C-24); 20,58 q (C-25); 51,67 q (C-26); 56,46 q (C-27); 52,26
?(C-28).
Qua ket qua phan tich cac pho NMR, cac s6 lieu pho chi tiet da dugc xSy dung va dua ra la chmh xac va hoan
toan phu hgp voi cau tnic ciia phan tii Vmcristin sulfat.
3.2.2.4. Ph6 khoi lugng (MS)
Ket qua xac dinh pho khoi ciia nguyen lieu Vincristm sulfat cho pic manh ion phan hi m/z 825,50 phii hgp vin
manh ion phan hr m/z cua Vmcristin chuta la 825,50. Nhu vay phan hi lugng ciia Vincristin sulfat la 825,50 ph4
hgp vcri khOi lugng phan hi ciia Vmciistin sulfat co cong tiiitc phan tii C^gHj^N^jO,,,

20 Tap chi KIEM NGHI$M THU6C - S6 1.2013; TJp 11.(39)

 wkj^Mmiii r uir I n IM
H
•)
•:

1i*^
r

,1
m ON OK KU Be B1 IW W BD BR BU

Hinh 7a. Pho MS cda VCR chudn mnh 7b. Pho MS cua nguyen lieu VCR
Kit lugn: Tir phdn tich thih ehit vd dii li§u phd UV-
Bdng 1. So sdnh kit qud tru&c vd sau hhi tinh che
VIS, IR, NMR vd MS k ^ hgp vdi so sanh vdi tdi li?u Vinblastin sulfat
tham khdo cd thd khdE^ dinh duge chit sau khi tinh chd ~'^^~..._Giai dogn
Id ^^cristin sulfat. Tnn/c khi tinh chi Sau khi tinh che
Chi H&u'~^^~.^
3.3. So sdnh kit qud kiim tra nguyin lieu trir&c vd sau Mit Vhhi lu^ng do
13,6 12,5
khitinhche Umkbd(%)
Tiing l^p< 1,1% Titag tap < 0,3%
3.3.1. Vinblastin sulfat Tap chit liSn quan
T6ng tap = 3,3% Tong tap = 0,6%
Sir dving didu ki?n phdn tich theo USP. 34. Nguyen H&m lirgmg (%)
lifu \^nblastin sulfat sau qud tiinh tinh che d^t ket qud 96,6 99,9
theo chat khan
so vdi trude khi tinh ehd nhu sau:

Hinh 8a. SKD xdc dinh tgp chdt lien quan cua nguyen Hinh 8b. SKD xdc dinh tgp chdt lien quan cua nguyen
lieu VBL trudc khi tinh che lieu VBL sau khi tinh che

Sau khi tinh chd nguydn lieu Vmblastin sulfat, mat Bdng 2. So sdnh kit qud tru&c vd sau khitinhche
khoi lugng do 1dm khd giam, so lugng cdc tap chit Vincristin sulfat
gidm tu 8 t9p xudng cdn 4 t^p vd ^ g cac tap chdt giam '~^—.^..^^^ Giai dogn
CM tieu~~~~~~~~...,_^^ Tru&c kla&ih dii Sau khitinhche
tu 3,3 % xudng 0,6 % vd bam lugng tang hi 96,6 % len
99,9 %. Nhu v^y qud tiinh tinh ch^ da lo^i dugc tap, Mat kbhi lirang do lam
9,4 8,4
1dm tang dg tinh khidt ciia boat chat. kho (%)
3.3.2. Vincristin sulfat Timgt9p< 1,9% Tmig t^tp < 0,7%
T9P ehkt li§n quan
T6ng Mip = 4,3% T6ng t9p = 2,0%
Su dvmg didu ki?n phdn tich theo USP. 34. Nguydn
Hkm lu^rng (%) theo chit
li$u Vinblastin sulfet sau qud trinh tinh chd d?t kdt qua khan
96,8 99.6
so vdi tiudc khi tmh chd nhu sau:

Tjp chi K I 4 M N G H I J M T H U 6 C - S4 1.2013; T|p 11.(39)

 oADi A.s^Jl^'l^nal-M},'l•^D tVWCRIVNCR[n/l>)

BOO'

_i_Jlii. i ,n «c .»

ffl/i/r Pa. 5/i2) jcac dinh tgp chdt lien quan cua nguyenHinh 9b. SKD xdc dinh tap chdt lien quan cua nguyen li^u
li?u VCR truac khi tinh che VCR sau khi dnh chi

Sau khi tinh ehd nguyen Ueu Vmcristin sulfat, mit khdi lugng do 1dm khd giam, tdng eac tap chat gidm tit
4,3% xudng 2,0% va bam lugng tdng tu 96,8% ldn 99,6%. Nhu vdy qud tiinh tinh chd da lo^i dugc tap, 1dm tdng
dd tinh khiet ciia boat chdt.
4. K^t luan
Qua thai gian nghien curu vd tiidn khai tiiuc nghidm, chiing tdi da dua ra dugc quy trinh tmh chd Vinblastin
sulfat va Vmcristin sulfat. Cdc quy trinh ddu ehi tidt, ro rang, khoa hgc, sii dung dung mdi it ddc hai, cho cdc sdn
phim dn dpih vd sd lugng (bieu suit) vd chat lugng.
Sdn phdm tiiu dugc sau khi tmh chd da duge xde dinh cau tiiic dua tidn phuong phap pho hong ngo^i, pho
UV-VIS, pho khdi lugng va phd NMR. Kdt qud khdng djnh cong tinic phdn bi eung nhu ciu tiiic cua nguyen li?u
tinh che dugc la Vinblastin sulfat vd Vincristin sulfat.
Hai nguyen lieu Vmblastm sulfat vd ^^cristin sulfat ttiih che dugc dat ydu edu dd thidt l§p chit doi chidu phyc
vp cho cong tdc Idem tra vd gidm sdt ehdt lugng thuoc tien thi trudng.

Tdi li^u tham khao

1. Dugc diin My 34 (2011).
2. Bg mdn Dugtc lieu, trucmg Dai hoc Dugc Ha Ngi (2007), Bai gidng dugc lieu tap 1-2, NXB Y hpc.
3. Trinh Van Lau, Thai Nguyen Himg Thu (2010), "Phuong phdp chiet, phan lap, tinh che, nhan dang vd thiet lap chat
chuan la chat dac tnmg tii dugc heu".
4. Vifn Hda hgc Cong nghiep Viet Nam (_2011), "Nghien c ^ qui trinh ban tdng hgrp 'S^cristin suliat vd Vinblastin sulfat
tir Vindolin va Catharanthin lam thuoc chong ung thu mdu".
5. Oishan Lin and Jinghua Zhu (2011), Determination of Vmcristine and Vinblastine in Catiiaranthus Roses Leaves by
Liquid Chromatography Mass Spectrometry.
SUMMARY
Vinblastine sulfate and Vincristine sulfate were purified by preparative HPLC Labomatic HD 3000 and reverse
column CIS LiehroPrep 60 x 500 mm, 15 - 25 pm.
The Vinblastine sulfate and Vincristine sulfate structure offinalproducts are confirmed by IR, UV-VIS. MS, and
spectroghraphy.
The content of Vinblastine sulfate and Vincristine sulfate obtained 99.9% and 99.6%, respectively (determin
HPLC). These products can be used to establish reference standards controling the quality of drugs.

Tsp chi KIEM NGHIEM THUOC - Si 1.2013; TSp 11.(39)