B Y T

TRNG I HC DC H NI

HN TH DNH
MSV : 1101078

NGHIN CU NG DNG PH CN
HNG NGOI NH LNG
NHANH MT S THUC VIN NN
CHA CEFUROXIME BNG THIT B
O PH CN HNG NGOI CM TAY
KHA LUN TT NGHIP DC S

H NI 2016

B Y T
TRNG I HC DC H NI

HN TH DNH
MSV: 1101078

NGHIN CU NG DNG PH CN
HNG NGOI NH LNG
NHANH MT S THUC VIN NN
CHA CEFUROXIME BNG THIT B
O PH CN HNG NGOI CM TAY
KHA LUN TT NGHIP DC S
Ngi hng dn:
1. Ths. Nguyn Lm Hng
2. DS. Bi Vn Trung
Ni thc hin:
1. Vin kim nghim thuc TW

H NI 2016

LI CM N
Em xin by t lng knh trng v bit n su sc n cc thy c v
ton th cn b, nhn vin trng i hc Dc H Ni to iu kin gip
ti trong sut thi gian hc tp v nghin cu.
hon thnh ti tt nghip ny ti xin chn thnh by t lng knh
trng v bit n su sc ti Ths. Nguyn Lm Hng lun tn tnh hng
dn, gip ng vin ti trong sut qu trnh thc hin v hon thnh ti
ca mnh.
Ti xin chn thnh cm n DS. Bi Vn Trung cng cc anh ch Khoa
Vt l o lng _ Vin kim nghim thuc TW to iu kin thun li v
hng dn tn tnh nhng kin thc thit thc gip em c th hon thnh tt
ti ny.
Mc d, em rt c gng hon thnh ti mt cch hon chnh
nht. Song, em vn cn nhng hn ch v kin thc v kinh nghim nn
khng th khng trnh khi nhng thiu st nht nh trong qu trnh hon
thnh ti cng nh qu trnh thc tp ti Vin. Em rt mong c nhn
nhng kin ng gp, ph bnh ca qu thy c v cc anh ch. l hnh
trang gip em hon thin bn thn c tt hn.
Cui cng, mt ln na em xin chn thnh cm n cc thy gio, c
gio, cc n v v c nhn gip trong qu trnh hc tp v thc hin
kha lun tt nghip ny.
Sinh vin
Hn Th Dnh

MC LC

DANH MC CC K HIU VIT TT

FT
NIR
IR
MIR
UV-VIS
SKS
% RSD

Fourier Transform
Near Infrared
Infrared
Mid Infrared
Ultravioletvisible

Bin i Fourier
Cn hng ngoi
Hng ngoi
Hng ngoi gia
T ngoi-kh kin
S kim sot
lch chun tng i

DANH MC CC BNG
Bng 3.1: Cng thc bo ch vin nn cha cefuroxime axetil theo cng thc
vin Haginate 500
Bng 3.2 : Cng thc bo ch vin placebo theo cng thc vin Haginate 500
Bng 3.3: Cng thc bo ch vin nn cha cefuroxime axetil theo cng thc
vin Pmz-Zanimex 250
Bng 3.4: Cng thc bo ch vin nn placebo theo cng thc vin
Pmz-Zanimex 250
Bng 3.5: Cng thc bo ch vin nn cha cefuroxime axetil theo cng thc
vin Cerzinate 250

Bng 3.6: Cng thc bo ch vin nn placebo theo cng thc vin Cerzinate
250
Bng 3.7: Hm lng cc vin m hnh theo cng thc Haginate 500
Bng 3.8: Hm lng cc vin m hnh theo cng thc Pmz-Zanimex 250
Bng 3.9: Hm lng cc vin m hnh theo cng thc Cerzinate 250
Bng 3.10: Kt qu kho st c hiu ca phng php
Bng 3.11: Kt qu thm nh ng ca phng php ng vi cng thc
Haginat 500
Bng 3.12: Kt qu thm nh ng ca phng php ng vi cng thc
Pmz-Zanimex 250
Bng 3.13: Kt qu thm nh ng ca phng php ng vi cng thc
Cerzinate 250
Bng 3.14: Kt qu thm nh lp li ca phng php ng vi cng thc
Haginate 500
Bng 3.15: Kt qu thm nh lp li ca phng php ng vi cng thc
Pmz- Zanimex 250
Bng 3.16: Kt qu thm nh lp li ca phng php ng vi cng thc
Cerzinate 250
Bng 3.17: Kt qu thm nh chnh xc trung gian ca phng php ng
vi cng thc Haginate 500
Bng 3.18: Kt qu thm nh chnh xc trung gian ca phng php ng
vi cng thc Pmz-Zanimex 250

Bng 3.19: Kt qu thm nh chnh xc trung gian ca phng php ng

vi cng thc Cerzinate 250
Bng 3.20: Kt qu phn tch thuc Haginate 500
Bng 3.21: Kt qu phn tch thuc Pmz-Zanimex 250
Bng 3.22: Kt qu phn tch thuc Cerzinate 250
DANH MC CC HNH
Hnh 1.1: Cng thc ha hc ca cefuroxime axetil

Hnh 1.2: S hnh thnh Peptidoglycan v v tr tc ng ca khng sinh

beta-lactam
Hnh 1.3 (a,b,c): M hnh cc kiu dao ng ha tr ca phn t
Hnh 1.4 (a,b,c): M hnh cc kiu dao ng un ca phn t
Hnh 1.5: Gin phn b th nng dao ng trong phn t
Hnh 1.6: Ph MIR o bng ATR v ph NIR o bng phn x khuch tn
ca Magie stearat
Hnh 1.7: My quang ph NIR o truyn qua
Hnh 1.8: My quang ph NIR o phn x
Hnh 1.9: My quang ph NIR thng
Hnh 1.10: My quang ph FT-NIR
Hnh 1.11: Phn tch ph NIR xuyn qua bao b
Hnh 1.12:Phn tch hng lot vin trn dy chuyn sn xut bng NIR
Hnh 3.1: S dp vin

Hnh 3.2: Thit b NIR cm tay

Hnh 3.3: ng tuyn tnh ca vin nn m hnh cha cefuroxime theo cng
thc vin Haginate 500
Hnh 3.4: ng tuyn tnh ca vin nn m hnh cha cefuroxime theo cng
thc vin Pmz-Zanimex 250
Hnh 3.5: ng tuyn tnh ca vin nn m hnh cha cefuroxime theo cng
thc vin Cerzinate 25

T VN
Thuc trn th trng Vit Nam ngy cng a dng v chng loi v
c sn xut vi s lng ln gy rt nhiu kh khn cho cng tc kim tra,
gim st v m bo cht lng thuc. c bit, vi cng ngh ngy cng
pht trin, thuc gi ngy cng c sn xut mt cch tinh vi, tr trn vo th
trng thuc di nhiu hnh thc khc nhau. Do , thuc gi, thuc km
cht lng ang l mt mi nguy him thng trc cho sc khe cng ng
v e da n li ch, uy tn ca cc cng ty sn xut dc phm chn chnh.

Cc phng php thng thng c s dng nh sc k lp mng (TLC),

sc k lng hiu nng cao (HPLC), sc k lng khi ph (LC_MS), quang
ph UV_Vis, IR cho kt qu vi chnh xc cao, nhng tn rt nhiu thi
gian, nhn lc,... phn tch v rt kh c th kim sot ht c cht lng
ca tt c cc thuc trn th trng.
Nm 1929, Alexander Fleming pht hin ra kh nng khng khun ca
nm Penicillium notatum, m u cho nghin cu v s dng khng sinh[3].
K t khi pht hin ra khng sinh Penicilline n nay hng trm loi khng
sinh v cc thuc tng t c pht minh v a vo s dng. S ra i
ca khng sinh nh du mt k nguyn mi ca y hc v iu tr cc bnh
nhim khun, cu sng hng triu triu ngi khi cc bnh nhim khun
nguy him, mt trong s nhng bnh ng hng u c v t l mc bnh v
t l t vong [1]. Mt vi nghin cu ch ra rng Cefuroxime- khng sinh
Cehalosroprin th h 2, nhm -lactam, hin ang l mt trong nhng loi
khng sinh c cc nh thuc, bnh vin, trung tm y t s dng ph bin v
rng ri [3]. Chnh v l do c s dng ph bin m tnh trng thuc gi
thuc km cht lng ngy cng gia tng.
Trc nhng thc trng trn, vn cp thit cn t ra l phi tm ra
c nhng phng php c th phn tch nhanh kim sot c ht cht
lng ca cc thuc trn th trng, nht l nhng thuc c nguy c cao b
lm gi. Ph cn hng ngoi c bit n t u th k XIX, nhng do s
pht trin mnh m sut mt thi gian di ca ph UV-VIS v ph hng ngoi
gia (MIR), gn y l s bng n ca cng ngh quang ph Raman m ph
NIR hu nh b lng qun [7]. Khong 30 nm tr li y, nh s ci tin v
cng ngh ca thit b NIR v h tr c lc ca phn mm phn tch, vai tr
quan trng ca ph NIR dn c pht huy [7] [11].

10

Phng php quang ph cn hng ngoi c bit n l k thut mi

mang nhng u im nh phn tch nhanh, khng ph hy mu, t phi chun
b mu, khng tn dung mi, ha cht, khng c hi... v c th p ng
c cc nhu cu cp thit hin nay. V vy, ti tm hiu, nghin cu v
chn ti: Nghin cu ng dng ph cn hng ngoi nh lng nhanh
mt s vin nn cha cefuroxime bng thit b o ph cn hng ngoi cm
lm ti cho bo co kha lun tt nghip ca mnh vi 4 mc tiu sau:
Xy dng c quy trnh phn tch cefuroxime bng phng php
quang ph cn hng ngoi trn mt s nn ch phm vin nn.
Thm nh quy trnh phn tch xy dng.
ng dng phn tch thuc trn th trng.

Chng 1. TNG QUAN

1.1. Tng quan v cefuroxime axetil
1.1.1. Danh php
Cng thc ha hc:

Hnh 1.1: Cng thc ha hc ca cefuroxime axetil

11

Cng thc phn t: C20H22N4O10S

Khi lng phn t: 510.475 g/mol
Tn khoa hc( IUPAC): (RS) 1R1-Acetoxyethyl (6R,7R)-3
[(carbamoyloxy)methyl]-7--8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2carboxylate.[4]
1.1.2. Tnh cht vt l
Cefuroxime axetil dng bt kt tinh trng hoc trng ng, t tan trong
nc, tan trong aceton, ethyl acetat v methanol, t tan trong ethanol.[15]
1.1.3. Cc dng bo ch v cch dng
Cefuroxim axetil: Dng thuc ung, liu biu th theo s lng tng
ng ca cefuroxim.
Hn dch ung 125 mg/5 ml; 250 mg/5 ml; vin nn: 125 mg, 250 mg,
500 mg [5].
1.1.4. C ch tc dng
Cefuroxim l khng sinh Cephalosporin th h 2, thuc nhm betalactam.Vch t bo vi khun ch yu c cu to t peptidoglycan, l thnh
phn quan trng m bo tnh vng chc ca t bo, v vy rt cn cho s tn
ti v pht trin ca t bo vi khun.
Qu trnh hnh thnh peptidogycan( gm 3 giai on): Peptidoglycan l
nhng polysaccharid mch thng gm cc chui disaccharid lp li, an cho
nhau bi cc peptid to thnh mt c cu ging nh mng li [2] :

12

Giai on 1: hnh thnh Uridin diphosphat(UDP)-acetylmuramin-pentapeptid.

Phn ng cui cng ca giai on ny l thm dipeptid D-alanyl-D-alanin vo
tn cng to thnh pentapeptid.
Giai on 2: phn ng kt hp UDP-acetylmuramin-pentapeptid v UDPacetylglucosamin thnh chui di.
Giai on 3: hon tt day ni ngang vi s c mt ca tranpeptidase.
Glycin(GI) tn cng trong cu pentaglycin ca pentapeptid th nht lin lin
kt vi D-alanin th 4 ca pentapeptid th 2 v gii phng ra D-alanin th 5.
C ch dit khun: Cc beta-lactam c kh nng acyl ha cc D-alanin
transpeptidase, c ch giai on cui ( giai on 3) ca qu trnh tng hp
vch t bo vi khun( giai on to lin kt ngang gia cc peptidoglycan.
Qu trnh sinh tng hp vch t bo b ngng li, vi khun khng c vch che
ch s b tiu dit.[2] [3]

13

Hnh 1.2: S hnh thnh Peptidoglycan v v tr tc ng ca khng sinh

beta-lactam
1.1.5. Tc dng dc l
Cefuroxim c hot tnh khng khun hu hiu v rt c trng chng
nhiu tc nhn gy bnh thng thng, k c cc chng tit beta lactamase/
cephalosporinase

ca

vi

khun

Gram

dng

Gram

m.

Cefuroxim c bit rt bn vi nhiu enzym beta - lactamase ca vi khun

Gram m.
Ph khng khun:
Cefuroxim c hot tnh khng cu khun Gram dng v Gram m a kh v
k kh, k c hu ht cc chng Staphylococcus tit penicilinase, v c hot
tnh khng vi khun ng rut Gram m.
Cu khun Gram(+):Staphylococcus aureus, Streptococcus pneumonia,
Streptococcus pyogenes, Anaerobic streptococci
Cu khun Gram(-): Nessieria gonorrhoeae
Vi khun hnh que Gram (-): Enterobacter aerogenes, Haemophilus
influenzae, Klebsiella pneumoniae , Escherichia Coli, Proteus mirabilis.
[5] [23]
1.1.6. Dc ng hc
Sau khi ung, cefuroxim axetil c hp thu qua ng tiu ha v
nhanh chng b thy phn nim mc rut v trong mu phng thch
cefuroxim vo h tun hon. Thuc c hp thu tt nht khi ung trong ba
n. Thuc t nng ti a 4 6 mg/lt vo khong 3 gi sau khi ung 250

14

mg hn dch. Nng nh trong huyt tng ca hn dch ung t trung

bnh 75% nng nh trong huyt tng ca thuc vin. Do , thuc vin
v hn dch ung cefuroxim axetil khng th thay th nhau theo tng quan
mg/mg. C ti 50% cefuroxim trong h tun hon lin kt vi protein huyt
tng. Na i ca thuc trong huyt tng khong 70 pht v di hn
ngi suy thn v tr s sinh.
Cefuroxim phn b rng khp c th, k c dch mng phi, m,
xng, hot dch v thy dch. Th tch phn b biu kin ngi ln khe
mnh nm trong khong t 9,3 - 15,8 lt/1,73 m2. Cefuroxim i qua hng ro
mu no khi mng - no b vim. Thuc qua nhau thai v c bi tit qua sa
m.
Cefuroxim khng b chuyn ha v c thi tr dng khng bin
i, khong 50% qua lc cu thn v khong 50% qua bi tit ng
thn.Thuc t nng cao trong nc tiu. Probenecid c ch thi tr
cefuroxim qua ng thn, lm cho nng cefuroxim trong huyt tng tng
cao v ko di hn. Cefuroxim ch thi tr qua mt vi lng rt nh.Nng
cefuroxim trong huyt thanh b gim khi thm tch.[5]
1.1.7. Ch nh
Thuc ung cefuroxim axetil c dng iu tr nhim khun th
nh n va ng h hp di, vim tai gia v vim xoang ti pht,vim
amian v vim hng ti pht do vi khun nhy cm gy ra. Cefuroxim axetil
cng c dng iu tr nhim khun ng tit niu khng bin chng,
v nhim khun da v m mm do cc vi khun nhy cm gy ra. Cefuroxim
axetil ung cng c dng iu tr bnh Lyme thi k u biu hin bng

15

triu

chng

ban

loang

do

Borrelia

burgdorferi

[5] [23]
1.1.8. Chng ch nh
Ngi bnh c tin s d ng vi khng sinh nhm cephalosporin.
1.1.9. Liu dng v cch dng
Cefuroxim axetil l mt acetoxymethyl ester dng theo ng ung
dng thuc vin hay hn dch.
Liu dng: 250mg hai ln mi ngy trong hu ht nhim khun bao
gm nhim khun ng h hp di t nh n trung bnh( v d vim ph
qun), tng gp i liu trong trong cc bnh nhim trung ng h hp di
nng hoc nghi ng vim phi. [5] [23] [18] [10]
Trong nhim trng ng tit niu: 125 mg hai ln mi ngy, gp i liu
trong vim b thn.
Tr hn 12 tui: 500 mg hai ln mi ngy trong 14-21 ngy (cho 28 ngy
trong bnh vim khp Lyme.
Tr em hn 3 thng tui: 125 mg hai ln mi ngy, nu cn tng gp i liu
i vi tr hn 2 tui vi vim tai gia, bnh Lyme.
Liu trnh iu tr thng thng l 7 ngy.[5] [23] [18] [10]
1.1.10.

Tc dng khng mong mun (ADR)

c tnh t l ADR khong 3% s ngi bnh iu tr.

Thng gp, ADR >1/100:
Ton thn: au rt ti ch v vim tnh mch huyt khi ti ni tim truyn.

16

Tiu ha: a chy.

Da: Ban da dng sn. [5]
1.1.11.
Cc phng php nh tnh , nh lng thng thng.
nh tnh.
A. Chit mt lng bt vin nghin mn tng ng vi khong 0,1 g
cefuroxim vi 5 ml dicloromethan (TT) v lc. Bc hi dch lc n thu c
cn. Ph hng ngoi ca cn phi ph hp vi ph i chiu ca cefuroxim
axetil hay vi ph ca cefuroxim axetil chun (Ph lc 4.2-[4])
B. Trong php th nh lng, trn sc k ca dung dch th hai pic chnh
(cefuroxim axetil diastereoisomer A v cefuroxim axetil diastereoisomer B)
phi c thi gian lu tng ng vi thi gian lu ca hai pic chnh trn sc k
ca dung dch chun.[4]
C. (tra thm dc in Anh, dc in M).
nh lng: Phng php sc k lng hiu nng cao ( HPLC)
iu kin sc k:
- Ct thp khng g (25 cm x 4,6 mm) c nhi pha tnh trimethylsilyl
-

silica gel dng cho sc k (5 m) (ct Hypersil SAS l ph hp).

Detector quang ph t ngoi t bc sng 278 nm.
Tc dng: 1,2 ml/pht.
Th tch tim: 20 l.
Pha ng: Hn hp 38 th tch methanol (TT) v 62 th tch dung dch
amoni dihydrophosphat 0,2 M.

(B sung ti liu, a v d v quy trnh

17

Nhn xt: u nhc im ca cc phng php trn: u im nhanh,

chnh xc, c hiu cao, nhc im, tn dung mi ha cht, tn thi
gian...)
1.2.

Tng quan v phng php quang ph cn hng ngoi

Ph cn hng ngoi c bit n t u th k XIX [15], nhng do s

pht trin mnh m sut mt thi gian di ca ph UV-VIS v ph hng ngoi

gia (MIR), gn y l s bng n ca cng ngh quang ph Raman m ph
NIR hu nh b lng qun [7]. Khong 30 nm tr li y, nh s ci tin v
cng ngh ca thit b NIR v h tr c lc ca phn mm phn tch, vai tr
quan trng ca ph NIR dn c pht huy [7] [11]. c nhiu nghin
cu c cng b cho thy ph NIR khng ch l cng c phn tch thng
quy m cn l cng c nghin cu quan trng, n cung cp nhng thng tin
quan trng v c nhng ng dng m khng th c c t bt k phng
php phn tch no khc.
1.2.1. Nguyn l c bn ca phng php quang ph NIR
Bc x cn hng ngoi (NIR) l cc bc x c bc sng t 780 nm
n 2500 nm nm trong vng hng ngoi [8] [11] [26]. Ph cn hng ngoi l
ph dao ng phn t, n khc vi ph Raman v ph hng ngoi gia (MIR)
[12] [16] [17]. tm hiu chi tit v ph NIR, chng ta cng tm hiu v m
hnh dao ng ca cc nguyn t trong phn t.
Cc lin kt trong phn t c cc kiu dao ng nh sau:
Dao ng dui ( Hnh 1.3): Gm dao ng dui i xng v khng i
xng. Do ng dui lm thay i khong cch gia cc nguyn t
trong phn t.

18

(a)

(b)

(c)
Hnh 1.3 (a,b,c): M hnh cc kiu dao ng ha tr ca phn t
Dao ng un ( Hnh 1.4): Un trong mt phng v ngoi mt phng.
Dao ng un lm thay i gc lin kt gia cc nguyn t trong phn
t.

19

(a)

(b)

(c)
Hnh 1.4 (a,b,c): M hnh cc kiu dao ng un ca phn t
Trong phn t, dao ng ca cc nguyn t cng tn ti cc trng thi
khc nhau, c xp theo bc da vo cc mc nng lng m chng tn ti
[11] [12] [17]. iu kin thng, chng dao ng trng thi c bn (bc
0) v cng ln bc cao, nng lng dao ng ca phn t cng ln.

20

Khi khong cch gia hai nguyn t (khi lng ln lt m1 v m2) trong lin
kt l re, tn s dao ng ca lin kt c cho bi cng thc:
e=

Trong

m=

m1 m2
m1+ m2

1
2

k
m

v k l h s n hi ca lin kt.

Nng lng dao ng thc t ca phn t c ngoi suy t php tnh gn

ng ca phng trnh Schrodinger, c gi l phng trnh th nng
Morse. Biu din phng trnh th nng y di dng s sng nh sau:
2

phng trnh trn,

( )

xe , ye

( )

l tn s gc dao ng tng ng vi trng thi

m khong cch hai nguyn t l r e;

ang xt;

1
1
1
e x e + + e y e + +
2
2
2

( )

E ( cm1 ) = e +

l cc hng s, trong

l s th t ca bc nng lng
e e x e e y e

Khi lm gn ng thm bc na, b bt s hng th ba, phng trnh c

dng l:
1
1
e x e +
2
2

( )

E ( cm1 ) = e +

( )

y l phng trnh gn ng ca biu thc th nng dao ng ca phn t

hay c s dng nht trong cc ti liu [11] [17].
Gin phn b nng lng nh sau:

21

Hnh 1.5: Gin phn b th nng dao ng trong phn t

T gin trn trn ta thy, khi tng tc vi cc bc x IR thch hp,
phn t s hp th mt phn nng lng chuyn ln trng thi dao ng
cao hn, kt qu l to nn cc di dch chuyn trn ph ca cht phn
tch. Cc chuyn dch xy ra t mc nng lng c bn (bc 0) ln trng thi
dao ng bc 1 th gi l cc di chuyn dch c bn. Cc dch chuyn xy ra
gia trng thi dao ng c bn v cc mc nng lng c bc cao hn (t
bc 2 tr ln) th c gi l cc overtone [11] [14] [17].
Cc dao ng rung lc, un v xoay d xy ra hn cc dao ng dc
theo trc v chng cn nng lng nh hn nng lng to cc overtone. Cc
bc x trong vng MIR v FIR to nn cc dch chuyn c bn. Bc x vng
FIR c bc sng di, nng lng yu, t lm thay i trng thi dao ng, c

22

chng ch lm thay i c cc tri thi rung lc n gin. Ph FIR t c

ng dng trong phn tch [17]
Cc bc x vng MIR c nng lng ph hp vi nhiu loi lin kt
nn rt d b hp th, cng cc di hp th ln. Mi lin kt hp th mt
di sng c trng khc nhau v tch bit nhau r rng. V th, mi di trong
ph MIR c trng cho tng kiu dao ng khc nhau ca mi lin kt khc
nhau. Tp hp cc di y (ph MIR) c hiu cho mt cht khc nhau. Trong
phn tch, ph MIR c xem l ph vn tay xc nh cc cht. Phn tch
ph MIR cn c th xc nh c cu trc phn t cc cht phn tch.
i vi cc bc x trong vng NIR, do c nng lng ln nn khi tng tc
vi phn t cht phn tch s c hai kh nng xy ra: Th nht, lm thay i
trng thi dao ng phn t t c bn ln cc bc cao 2,3,4 to nn
overtone; th hai, lm cc dao ng c bn khc nhau trong phn t xy ra
ng thi. Bi vy, ph NIR chnh l s kt hp ca cc di dch chuyn bi
tn v cc di dch chuyn c bn. Cc di ph trong vng NIR c s chng
chp ln nhau nn hnh dng ph t, khng tch bit c cc di hp th cho
tng kiu lin kt. Thm vo , cng ph NIR l thp hn rt nhiu so
vi ph MIR nn so vi ph MIR v ph Raman, ph NIR c c hiu
khng cao [11] [14].
Overtone thng xy ra cc bc sng ngn trong vng NIR v c
trng cho cc lin kt X-H (c th l C-H, S-H, N-H v O-H). Overtone bc
cng cao th cng kh xy ra hn, cng ph hp th cng yu hn. Trn
ph NIR, overtone c cng thp hn t 10 n 1000 ln so vi cng
ca cc di dch chuyn c bn. [11] [14] [26]

23

Hnh 1.6: Ph MIR o bng ATR v ph NIR o bng phn x khuch tn

ca Magie stearat
Tuy khng c hiu nh vy, nhng cng v nng lng ln, t l hp th xy
ra t nn bc x NIR c th xuyn su hn vo mu phn tch, mang nhiu
thng tin v mu phn tch hn, gip chng ta c th o c ph thng qua
bao b trong sut nh thy tinh, polymer to nn cc u vit ca ph NIR
[26]. Cc ng dng ph NIR s tip tc c trnh by cc mc sau.
1.2.2. Cc k thut o ph NIR
C ba k thut o ph NIR l: Truyn qua, phn x truyn qua v
phn x khuch tn.
K thut o truyn qua v phn x truyn qua c cng bn cht, u
da trn vic xc nh t l cng ca chm bc x trc v sau khi truyn
qua mu phn tch. T l y ph thuc vo hp th ring ca phn t ,
nng cht phn tch C v quang trnh l khi bc x i qua mu. Chng tun
theo nh lut Lambert Beer:
A=lC =log 10

I
I0

( )

24

Trong , I v I0 l cng bc x trc v sau tng tc vi cht phn tch.

Cc k thut ny khi o phi chun b mu, tn nhiu thi gian. Nu mun
nh lng th phi n nh c quang trnh ( dy mu v gc chiu), ph
thuc vo bn cht tng mu o (mi mu c khong tuyn tnh khc nhau)
So vi ph hng ngoi v Raman trn phng din nh tnh, n khng c
hiu bng. V mt nh lng, n c p dng cho cc cht lng, tuy nhin
so vi ph UV-VIS th chnh xc khng cao. Chnh v th cc k thut ny
t c s dng.
Trong k thut o phn x khuch tn, ngi ta xy dng ph da trn
t l R ca cng nh sng sau khi phn x qua mu o I vi cng nh
sng phn x qua b mt nn chun hoc nn mu IR:
R=

I
IR

Khi thm nhp vo cht phn tch, bc x NIR truyn mt phn nng lng
lm thay i trng thi dao ng ca phn t. Phn nng lng cn li c
truyn n detector. S chnh lch cng gia nh sng phn x bi nn
mu v nh sng phn x thu c t mu phn tch to nn hp th gi
log10(1/R) tng bc sng tng ng [11] [26] . Ph c xy dng t
s thay i hp th gi theo bc sng ca mu phn tch c gi l
ph NIR ca cht y.
So vi cc k thut trn, k thut o phn x khuch tn ang cho thy
nhiu u th:
Th nht, php o phn x khuch tn khng ph thuc vo dy,
quang trnh ca cht phn tch m ch ph thuc vo bn cht v t l ca cht
phn tch trong mu phn tch. i vi cc mu o rn, ngi ta chiu trc
tip bc x NIR vo mu o. i vi cc mu lng, ngi ta thit k thm

25

cc ht nh phn x nh sng cho vo dung dch (quicksand), bc x NIR

khi chiu vo dung dch, sau khi tng tc vi cht phn tch dng dung
dch, tn hiu u ra c phn x li v vn mang thng tin v cht phn tch.
iu ny gip chng ta c th phn tch nhanh m khng cn hoc rt t phi
chun b mu trong qu trnh phn tch, tit kim thi gian, chi ph, khng cn
nhiu ph kin tr gip (cu vt, cc o), gim sai s do cc yu t ngoi lai
v tng chnh xc ca php o.
Th hai, cc phn mm phn tch ph hin nay s dng phng php
bnh phng ti thiu tng phn ti nhiu bc sng (Partial least square PLS), phng php phn tch lm tri thnh phn (Principal component
analysis) cho php nh lng c cc thnh phn cht phn tch da vo s
thay i t l p ng ca n trong nn mu. Khi thay i nng cht phn
tch, t l hp th ca nn mu v ca cht phn tch ti cc im khc
nhau cng thay i theo. Da vo s thay i y, chng ta c th thit lp
c ng chun t ph cht phn tch v nng tng ng. Khi c s
thay i v iu kin o, t l cng gia cc nh vn khng thay i
nhiu nn ng chun c xy dng kh chnh xc, t b nh hng bi cc
thay i nh trong qu trnh o. S dng ng chun y, chng ta o ph
ca cht phn tch v c th xc nh c ngay hm lng ca cht phn tch
trong mu.
1.2.3. Thit b
1.2.3.1. Nguyn tc cu to
V c bn, my quang ph NIR cu to bi cc b phn sau: Ngun
sng, h quang, b phn ng mu v detector. Ty theo kiu o m v tr ca
detector c b tr khc nhau nh hnh di.

26

Hnh 1.7: My quang ph NIR o truyn qua

Hnh 1.8: My quang ph NIR o phn x

Ngun NIR
n NIR c trng c s dng trong cc thit b FT-NIR l n
halogen vi cng sut ngun t 5 w n 50 w. i vi cc n NIR, n cng
s dng nhit thp th tui th cng c ko di v u im ca cc loi
n ny l c th s dng cng sut thp nn tui th n c tng ln [11]
[14] [20].
H quang
My quang ph NIR v my quang ph FT-NIR c cu to khc h
quang.
My quang ph NIR thng thng: Loi ph bin nht ang c lu
hnh c cu to gm:

27

Hnh 1.9: My quang ph NIR thng

+ B phn n sc: H thng thu knh kt hp vi lng knh hoc cch t.
+ B phn iu tit quang m (acousto-optic tunable filter (AOTF)).
My quang ph FT-NIR: S dng h giao thoa k Michelson v ngun
laser:

Hnh 1.10: My quang ph FT-NIR

28

+ Giao thoa k Michelso gm: Gng c nh; gng i ng v b phn

tch chm tia (lm bng thch anh, CaF2 hoc KBr c ph lp bn m thch
hp).
+ Ngun laser: V c cu to phc tp, c bit l gng i ng lun di
chuyn trong qu trnh lm vic nn cc b phn c th khng khp vi nhau
trong qu trnh lm vic. Ngi ta phi s dng ngun laser cn chnh
chnh xc ca my v bc sng. Ngun laser thng c s dng l HeNe
(~ 633 nm).
Detector
Cc thit b phn tch NIR c th qut vi tc cao, c bit l cc
thit b FT-NIR nn nhng detector p ng nhanh c u tin s dng. Cc
detector ny phi c lm lnh khi lm vic bng pin nhit in (TE) hoc
nitrogen lng. Mt s loi detector ph bin cho thit b ny l InSb, MCT v
InGaAs. Trong detector InGaAs kt hp lm lnh bng pin peltier vi
tuyn tnh cao, nhy cao v kh nng p ng nhanh l loi c dng ph
bin nht hin nay [11] [22].
B phn ng mu
Thit b o phn x khuch tn s dng ca s thch anh [11]
Thit b o truyn qua s dng cu-vt o bng thy tinh hoc thch anh
[11].
Mt s thit b o s dng ch phn x truyn qua c thit k b
phn ng mu kiu si quang nhm tng quang trnh, tng kh nng
tng tc ca mu v bc x NIR, gim bt sai s v quang trnh.[11]
[14]
1.2.3.2. Nguyn tc hot ng
Nguyn tc hot ng chung ca my quang ph NIR cng tng t
nh my quang ph MIR. Chm tia sng t ngun i vo h quang c tch

29

thnh cc di ph n sc hoc c bin iu thnh cc c trng ring cho

mi loi tia n sc. Sau khi qua h quang, bc x ny c chia lm hai
phn bng gng bn m hoc gng quay. Mt phn cc bc x ny tip tc
ti v tng tc vi mu phn tch, phn cn li ti thng detector. Bng cch
ghi nhn, s ha v so snh tn hiu ti trc tip v tn hiu sau tng tc,
ngi ta thit lp nn ph NIR ca cc cht phn tch. Cc phn mm hin
nay cho php x l ph sau phn tch, xy dng th vin ph chun, so snh
ph nh tnh v c cc thut ton ring thit lp phng php nh
lng cc thnh phn mu phn tch [11] [14].
Ngoi cc nguyn tc chung trn, cc loi my NIR c nguyn l hot ng
ring khc nhau.
My quang ph NIR thng
nh sng t ngun sau khi vo h quang qua h thu knh gng gp
sau i qua lng knh hoc cch t nhiu x s c tch ra thnh di sng
c bc sng tng (hoc gim) dn. Di sng ny c chuyn qua b phn
lc quang m AOTF. Nh b lc ny, cc vng nh sng ln lt c chn
v chuyn tip tng tc vi mu phn tch. Detector ghi nhn v phn tch
ln lt tng vng nh sng khc nhau cho ta ph NIR ca cht phn tch.
Ph NIR thu c ca ton di l kt qu ca s tng hp ph ca cc vng
lin tip nhau [11]
My quang ph FT-NIR
Cc bc x NIR t ngun sng c truyn qua ng chun trc vo
giao thoa k, chng b gng bn m tch ra lm hai phn nh nhau. Mt
phn ti gng c nh v mt phn ti gng di ng. Gng di ng di
chuyn vi vn tc thch hp (thng l 0,633 cm/s), lm cho tn s ca
chm tia sng phn x ti b bin iu ng thi c s thay i quang trnh

30

(hoc khc pha) so vi chm tia phn x ti gng c nh [11] [22]. Chm
sng phn x t hai gng sau khi kt hp vi nhau s giao thoa lm cho tn
hiu u ra thay i v c trng ring cho tng bc sng khc nhau. Qu
trnh nh vy c gi l qu trnh bin i Fourier. Trong my quang ph
FT-NIR, tt c cc bc x qua h quang c bin iu ng thi, chuyn qua
tng tc vi mu phn tch ng thi nn detector thit k cho loi my ny
cn s dng loi detector p ng nhanh, nhy cao [11] [22].
Ngun laser gip cn chnh chnh xc ca h quang v bc sng trc
mi qu trnh lm vic. Tn hiu laser c bin iu tn s 20 kHz, p
ng ca detector v cht phn tch c ghi nhn ti cc thi im m tn hiu
laser bng 0.
1.2.4. u nhc im ca phng php quang ph NIR
1.2.4.1. u im
Ph NIR c nng lng ln, c th i su vo trong mu phn tch,
mang thng tin ca cht phn tch, m bo c s ng u bn
trong mu phn tch.
Bng k thut o phn x khuch tn, c th o mu trc tip, khng
cn ph hy mu, tit kim thm thi gian phn tch, c bit c th
kim sot cht lng thuc ngay trong quy trnh sn xut kn.
Thi gian phn tch nhanh (khng qu 30 giy), gip phn tch c
nhiu mu, rt hiu qu trong cng tc sng lc nhanh thuc gi.
Va c th ng dng nh tnh, va c th ng dng nh lng mu
trc tip, chnh xc cao.
o c nhiu dng mu, nhiu dng bo ch khc nhau.
So vi phng php ph MIR, ph NIR t b nh hng bi iu kin
mi trng hn nn n nh ca php phn tch cao hn.
So vi phng php ph UV-VIS, ph NIR c hiu hn. Ph UV ch
o c dung dch lng nng thch hp, ph NIR c th o trc

31

tip mu m khng cn hoc rt t chun b mu, xc nh c cc

mu c hm lng ln, o c c cht rn, bt, lng, hn dch.
So vi phng php quang ph Raman, do im thu ph c kch thc
ln hn nn thng tin thu c t cht phn tch c tnh ng u cao
nn php nh tnh mang y thng tin hn, php nh lng chnh
xc hn. Php nh lng mu rn bng phng php NIR chnh xc
hn php nh lng bng phng php quang ph Raman . [19] [24]
1.2.4.2. Nhc im
c hiu cho php nh tnh dc cht l khng cao, gii hn pht
hin thp. Khng th hin c c trng ca cc thnh phn chnh bn
trong nn mu gm hn hp nhiu cht phn tch.
K thut phn tch kh phc tp, cng tc xy dng ng chun nh
lng cho tng loi mu l khc nhau, cn t m, cn thn v chnh xc
th php phn tch sau mi m bo c.
Cn phi cn chnh li my trc khi tin hnh nh lng cho kt
qu chnh xc. [19] [24]
1.2.5. Cc yu t nh hng n ph NIR
Nhit mu phn tch: Nhit cao lm mt s phn t cht phn
tch dao ng cc trng thi kch thch. Khi tng tc vi cht phn
tch, ph NIR a cc trng thi dao ng y chuyn ln mc cao hn.
Tuy nhin theo phng trnh th nng Morse, nng lng chuyn dch
gia cc mc khc nhau l khc nhau. Bc sng kch thch ca cc
mc nng lng khc nhau l khc nhau. Chnh v th, nhit nh
hng kh nhiu n ph NIR ca cht phn tch.
m v d lng dung mi: Lin kt O-H l mt trong nhng lin
kt c trng ca ph NIR. iu kin m v d lng dung mi
trong mu phn tch khc nhau s lm thay i ph NIR ca cht phn
tch.

32

dy mu o: Trong k thut o truyn qua v phn x truyn qua,

dy mu nh hng rt nhiu nn ngi ta thng c nh dy
mu o bng cch ng mu o trong cc cc o hoc cu vt c dy
khng i. Trong k thut o phn x khuch tan, xm nhp ca bc
x NIR l rt nh nn ch cn mu o khng qu mng bc x NIR
xuyn qua l c.
ng u ca mu o: i vi cc mu o dng dung dch, ng
u lun c m bo. Do kch thc vng o l c hn, nn ng
u ca mu o i vi cc mu dng rn, bt, hn dch l rt quan
trng. Mu cng ng u, php o cng chnh xc, ph thu c cng
th hin c nhiu thng tin ca cht phn tch, kt qu nh lng
cng ng.
S thay i dng th hnh: cc dng th hnh khc nhau, trng thi
dao ng ca cc phn t khc nhau, s tng tc vi bc x NIR l
khc nhau. i vi cc phn t hp th NIR mnh, nhiu cht s
chuyn dng th hnh trong qu trnh phn tch. Khi phn tch cn
s thay i ny v a tt c cc mu o v cng mt iu kin.
n nh ca mu o: Cc mu phn tch c tui th nht nh, sau
thi gian di chng c th b phn hy hoc thay i trng thi, nht l
cc vt liu chun. S thay i v cu trc hoc dng th hnh s nh
hng n kt qu o ph. Cn kim tra k lng trc khi tin hnh
phn tch. i vi cc vt liu chun, phi thay th hoc i hiu chun
khi n thi hn khuyn co.
1.2.6. ng dng ph NIR
ng dng trong cc sn phm nng - lm nghip
Quang ph cn hng ngoi c p dng nh lng cc thnh phn
ca sn phm nng lm nghip nh m, hm lng du, m, axit t do,
protein, carbonhydratemt cch ng tin cy, nhanh chng m khng cn

33

ph hy mu v khng tn km. T , ta xy dng quy trnh ti u trc tip

trong qu trnh gieo trng n thu hoch sn phm; kim tra, nh gi cht
lng thc n vt nui trong tng giai on t cht lng v hiu qu. [9]
ng dng trong cng nghip ha du
Ch s octan l mt i lng quy c c trng cho tnh chng kch
n ca nhin liu. Ch s ny c o bng t l phn trm th tch isooctane
c trong hn hp ca n vi n-heptan v c kh nng chng kch n tng
ng kh nng chng kch n ca nhin liu th nghim iu kin chun.
NIR c chng minh l c kh nng o ch s octan trong thi gian ngn.
Mt s nh my lc du v ang bt u ci t cc cng c gim st NIR
bng si quang hc kim sot qu trnh pha trn [24].Trong nhiu trng
hp NIR c th h tr vic phn tch hoc kim sot cc cp oxy ha trong
nhin liu. NIR c s dng theo di phn trm cc cht thm, phn
trm bo ha v im ng bng trong nhin liu hng khng JP-4. Trong mt
nghin cu, NIR c s dng phn tch mt tp hp ca 359 mu xng
v ch s octan nghin cu (RON), ch s octan ng c (MON), cht thm,
olefin, bo ho, MTBE, EtOH, oxy, benzen v lu hunh. [25]
ng dng trong thc phm ung
ng dng NIRS theo di lng ancol trong qu trnh ln men, m
trong thc phm v ung; xc nh lng cht bo, protein, lactose trong
cc sn phm sa[13]. NIRS nh gi sn phm ngay trn dy chuyn sn
xut thay v s dng cc mu trong phng qun l cht lng vi tc
nhanh[24].
ng dng trong cng ngh mi trng

34

Kt hp vi kh nng nhn dng vt cht ca my quang ph cn hng

ngoi v phn mm nhn dng c th phn bit gia cc nhm hoc cc loa
vt liu khc nhau. C th nh phn bit gia nc vi cc ancol, cc
hydrocarbon, dung mi hu c da vo ph c trng.
Hn na, phn mm c kh nng pht hin mt vt liu c th trong
cng nhm vt liu. V d, ng dng pht hin trong nhm du nhin liu
gm du diesel, du la, nhin liu my bay phn lc T , my quang
ph cn hng ngoi c ng dng trong pht hin nhanh cc hp cht hu
c trong x l nc thi. [6]
ng dng trong y t
ng dng y t ca NIRS l xc nh nng Glucoz, hm lng oxy
ca Hemoglobin trong mu; c th o bo ha oxy tnh mch (SVO 2),
c xc nh bi cung lng tim, cng nh cc thng s khc ( FiO 2,
hemoglobin, s hp th oxy). NIRS l mt k thut hu ch cho s pht hin
thay i mch mu, xc nh cc thnh phn protein lin quan n bnh tim
mch, xc nh thnh phn ha hc ca cc m x va ng mch [21]. NIRS
l k thut thch hp vi bnh nhn bi s khng xm ln, khng au v bc
x khng ion ha.
ng dng trong ngnh Dc
T bn cht ph v k thut o ph, phng php phn tch ph NIR
c mt s ng dng in hnh sau:
nh tnh

nh lng

35

+ nh tnh nguyn liu; t

+ Xc nh m trong

dc, bao b ng

nguyn liu, thnh phm

+ Nhn dng thnh phm

+ Xc nh hm lng dc

thuc dng phn liu

cht, t dc dng bo ch

+ nh tnh dc cht trong

+ nh lng cc thnh phn

cc dng bo ch

ca dung dch

Hnh 1.11: Phn tch ph NIR xuyn qua bao b

Hnh 1.12: Phn tch hng lot vin trn dy chuyn sn xut bng NIR

Chng 2: I TNG V PHNG PHP NGHIN CU

2.1.

i tng

36

Nghin cu xy dng quy trnh phn tch thuc cha cefuroxime axetil
bng phng php quang ph cn hng ngoi.
2.2. Nguyn liu, thit b
2.2.1. Nguyn liu
Cht chun: Cefuroxime axetil ( 814.5 g C16H16N4O8S mg/g, tnh
theo ch phm nguyn trng, SKS: 2010167.02).
Mu th
STT

Mu

Nh sn xut S l

SK

Hn dng

sn xut
1

Haginat 500

Cng ty c

030715

phn Dc

VD-17849- 30/07/18
12

hu giang
2

Pms-Zanimex

Imexpharm

250

Cerzinate 250

Cng ty c
phn Dc

060215

VD-859909

phm TW 25
( UPHACE)

T dc
STT

T dc

Nh sn xut

Lactose

Vit Nam

Sodium crosscarmelose

Trung Quc

Kollidon VA64

Trung Quc

Cellulose vi tinh th

Trung Quc

26/02/17

37

Aerosil

Trung Quc

Talc

Trung Quc

Magnesium stearate

Trung Quc

Sodium starch glycolate

Trung Quc

Sodium lauryl sulfate

Vit Nam

10

Polyplasdon XL

Trung Quc

11

Povidon

Trung Quc

12

DST

Trung quc

2.2.2. Thit b
ST

Tn thit b

M thit b

Hn hiu chun

T
1

My quang ph NIR cm

VKN/VL/05.01

10/2016

2
3

tay
Cn phn tch
My dp vin

VKN/VL/01.18
09/2016
Km my quang ph NIR

2.3. Phng php nghin cu

2.3.1. Xy dng quy trnh phn tch
Thu thp ti liu trong nc v nc ngoi lin quan n i tng
nghin cu. Tham kho phng php v k thut phn tch ca cc
nc tin tin trn th gii v ph NIR v cc ng dng ca n trong
phn tch dc phm.
Nghin cu cch thc s dng, trin khai phn mm trn thit b: Hiu
chnh thit b, cch xc nh ph, x l s liu, thit lp cng thc so
snh ph nh tnh, nh lng. Cch thit lp th vin ph chun,
to th vin ph chun.
Kho st iu kin o tng ng vi dc cht, xy dng quy trnh
phn tch thuc.
a ra c quy trnh phn tch.
2.3.2. Thm nh quy trnh phn tch

38

nh gi: c hiu, tuyn tnh, ng, lp li, chnh xc

trung gian ca quy trnh va thit lp trn mt s nn mu.
2.4. Ni dung nghin cu
2.4.1. Quy trnh phn tch
Xy dng cng thc vin m hnh c hm lng thay i xung quanh

vin hm lng thc t.

Xy dng vin c hm lng thc t, vin placebo.
iu kin o ph:
- Di o: t 6250 cm-1 n 4167 cm-1
- phn gii: 12 cm-1
- nhit : 20 - 30 C
- m: 60%
- S ln qut: 5 ln trong 1 ln thu ph
- Phn mm phn tch: Method Generator
o ph vin m hnh, t tn v lu th vin ph chun.
Thit lp xy dng ng chun to phng php nh lng trn thit

b.
nh lng cc mu th: Haginat 500, pms-Zanimex 500, Cerzinate
250
2.4.2. Thm nh quy trnh phn tch
Cc ch tiu cn thm nh bao gm: c hiu, tuyn tnh,
ng, lp li, chnh xc trung gian.
Ch tiu
thm inh
c hiu

Cch xc nh/ nh gi
Kim tra vin placebo

Gii hn chp nhn

Hm lng cefuroxime
axetil trong vin placebo
so vi hm lng vin
thc t cng thc tng
ng khng qu 2%

39

tuyn tnh H s tng quan

R 0,99 [26]

ng

Kim tra cc thuc c hm

T l thu hi : 98,0 %

lng thay i xung quanh

102,0 %

vin thc t xy dng

% RSD 2,0 %

c.
lp li

Xc nh gi tr RSD kt qu

% RSD 2,0 % (n = 6)

nh lng
chnh xc

Xc nh gi tr RSD kt qu

trung gian

nh lng gia 2 kim

% RSD 3,0% (n = 12)

nghim vin

Chng 3: THC NGHIM, KT QU V BN LUN

3.1. Thc nghim
3.1.1. Xy dng cng thc vin v dp vin
To vin nn m hnh vi hm lng ph bin trn th trng, da trn
cc cng thc thc t ca cc thuc trn th trng: Haginat 500mg,
Pmz-Zanimex 250, Cerzinate 250.
To cc vin nn c hm lng tng ng thay i xung quanh hm
lng ca cc cng thc vin m hnh.
S dp vin:

40

Hnh 3.1: S dp vin

3.1.2. Tin hnh
iu kin tin hnh:

41

Hnh 3.2: Thit b NIR cm tay

- My quang ph cn hng ngoi cm tay Micro Phazir, khoa Vt l
-

o lng, Vin Kim nghim thuc TW

Ch o: Phn x khuch tn, thu ph trc tip trn vin
Di o: 6250 cm-1 -4167 cm-1
phn gii: 12 cm-1
Nhit : 20-30C
m: 60%
S ln qut: 5 ln trong 1 ln thu ph
Phn mm phn tch: Method Generator
Tin hnh:
o ph ca cc mu vin m hnh v vin c hm lng thay i,

mi nng o 05 vin;
- Lu d liu cc ph phn tch;
- Thit lp th vin ph chun ca cc vin m hnh;
- Thit lp ng chun ph tng ng vi mi vin m hnh da trn
hm lng (%) v ph NIR thu c
- o ph ca cc vin trn th trng;
- Xc nh hm lng (% kl/kl) ca cefuroxime axetil trong mi vin, t
tnh ra hm lng thc t ca vin trn th trng.
3.2. Kt qu
3.2.1. Cng thc cc vin nn m hnh ca cc ch phm trn th trng
3.2.1.1. Cng thc vin Haginat 500

42

Cng thc cho vin nn cha Cefuroxime axetil

ST

Thnh phn

Lng (mg)/vin

T
1

Cefuroxime axetil

602

Aerosil

Polyplasdon XL

68

Natrilauryl sulfat

20

Sodium starch glycolate

142

Magnesium stearate

Talc

10

Kollidon VA64

48

Hm lng

66.59 %

Bng 3.1: Cng thc bo ch vin nn cha cefuroxime axetil theo cng thc
vin Haginate 500
Cng thc cho vin Placebo
ST

Thnh phn

Lng (mg)/vin

T
1

Aerosil

Polyplasdon XL

68

Sodium lauryl sulfate

20

Sodium starch glycolate

142

Magnesium stearate

Talc

10

43

Kollidon VA64

48

Bng 3.2 : Cng thc bo ch vin placebo theo cng thc vin Haginate 500
3.2.1.2. Cng thc vin Pmz-Zanimex 250
Cng thc cho vin nn cha Cefuroxime axetil
ST

Thnh phn

Lng (mg)/vin

T
1

Cefuroxime axetil

301

Aerosil

DST

30

Cellulose vi tinh th

30

Sodium lauryl sulfate

Talc

105

Magnesium stearate

1.5

Hm lng

63.44 %

Bng 3.3: Cng thc bo ch vin nn cha cefuroxime axetil theo cng thc
vin Pmz-Zanimex 250

Cng thc cho vin Placebo

ST

Thnh phn

Lng (mg)/vin

T
1

Aerosil

DST

30

44

Cellulose vi tinh the

30

Sodium lauryl sulfate

Talc

105

Magnesium stearate

1.5

Bng 3.4: Cng thc bo ch vin nn placebo theo cng thc vin
Pmz-Zanimex 250
3.2.1.3. Cng thc vin Cerzinate 250
Cng thc cho vin cha Cefuroxime axetil
ST

Thnh phn

Lng (mg)/vin

T
1

Cefuroxime axetil

301

Lactose

50

Sodium starch glycolate

55

Povidon

Aerosil

55

Sodium crosscarmelose

15

Magnesium stearate

Hm lng

62.19 %

Bng 3.5: Cng thc bo ch vin nn cha cefuroxime axetil theo cng thc
vin Cerzinate 250
Cng thc cho vin placebo

45

ST

Thnh phn

Lng (mg)/vin

T
1

Lactose

50

Sodium starch glycolate

55

Povidon

Aerosil

55

Sodium crosscarmelose

15

Magnesium stearate

Bng 3.6: Cng thc bo ch vin nn placebo theo cng thc vin Cerzinate
250
3.2.2. Thit lp ng tuyn tnh NIR ca cc vin nn m hnh cha
cefuroxeime axetil theo cc cng thc.
Thit lp ng tuyn tnh ca cc vin nn m hnh
Trn cefuroxime axetil chun vo mu placebo tng ng (3 mu
placebo) thu c hn hp bt c hm lng cefuroxime axetil thay
i xung quanh vin hm lng thc t, dp vin.
Cng thc tnh nng ca cefuroxime theo %:

mC: khi lng ca cefuroxime axetil nguyn liu( g)

mP: khi lng ca placeb( g)
3.2.2.1. Thit lp ng tuyn tnh ca cng thc Haginat 500

46

Trn cefuroxime axetil v placebo theo cc hm lng xung quanh hm

lng vin thc t Haginat 500.
Kt qu c th hin bng sau:
Khi lng
STT

Cefuroxime axetil
(mg)

Khi lng

Hm lng %

placebo (mg)

Cefuroxime axetil

0.5014

0.5008

50.03

0.6053

0.3997

60.23

0.7003

0.2997

70.03

0.8043

0.2035

79.81

0.9045

0.101

89.96

Bng 3.7: Hm lng cc vin m hnh theo cng thc Haginate 500
ng tuyn tnh

47

Hnh 3.3: ng tuyn tnh ca vin nn m hnh cha cefuroxime theo cng
thc vin Haginate 500
3.2.2.2. ng tuyn tnh ca cng thc Pmz- Zanimex 250
Trn cefuroxime axetil v placebo theo cc hm lng xung quanh
hm lng vin thc t Pmz-Zanimex 250
Kt qu c th hin bng sau:
Khi lng
STT

Cefuroxime axetil
(mg)

Khi lng
placebo (mg)

Hm lng
Cefuroxime axetil
(%)

0.4483

0.5483

44.98

0.5493

0.4500

54.97

0.6493

0.3544

64.69

0.75

0.2523

74.83

0.8498

0.1524

84.79

48

Bng 3.8: Hm lng cc vin m hnh theo cng thc Pmz-Zanimex 250
ng tuyn tnh:

Hnh 3.4: ng tuyn tnh ca vin nn m hnh cha cefuroxime theo

cng thc vin Pmz-Zanimex 250
3.2.2.3. Thit lp ng tuyn tnh ca cng thc Cezinate 250
Trn cefuroxime axetil v placebo theo cc hm lng xung quanh hm
lng vin thc t Cerzinate 250
Kt qu c th hin bng sau:
STT

Khi lng

Khi lng

Hm lng %

Cefuroxime axetil

placebo (mg)

Cefuroxime axetil

(mg)

49

(mg/g)
1

0.4068

0.6002

40.40

0.5008

0.5022

49.93

0.6036

0.3981

60.26

0.7034

0.3075

69.58

0.8051

0.2033

79.84

Bng 3.9: Hm lng cc vin m hnh theo cng thc Cerzinate 250
ng tuyn tnh:

Hnh 3.5: ng tuyn tnh ca vin nn m hnh cha cefuroxime theo

cng thc vin Cerzinate 250
3.3. Kt qu thm nh quy trnh phn tch
3.3.1. tuyn tnh

50

Thc nghim:
- Xy dng cc vin m hnh c hm lng thay i xung quanh hm
lng thc t.
- o ph vin m hnh, t tn v lu th vin ph chun.
- Thit lp c ng tuyn tnh ca tng cng thc.
ng chun ca cng thc Haginat 500
tuyn tnh mang li kt qu chnh xc vi h s tng quan cao R =
0,9985 v cc sai s hiu chun thp vi cn bc hai trung bnh bnh phng
sai s (RMSEC) l 0.6553
ng chun ca cng thc Pmz- Zanimex 250
tuyn tnh mang li kt qu chnh xc vi h s tng quan cao R =
0,9995 v cc sai s hiu chun thp vi cn bc hai sai s bnh phng trung
bnh (RMSEC) l 0.4415
ng chun ca cng thc Cerzinate 250
tuyn tnh mang li kt qu chnh xc vi h s tng quan cao R =
0,9995 v cc sai s hiu chun thp vi cn bc hai sai s bnh phng trung
bnh (RMSEC) l 0.3725.
Nhn xt: Cc ng tuyn tnh u c h s R > 0.99 => Phng
php nh lng t yu cu v tuyn tnh
3.3.2. c hiu
Thc nghim: Dng phng php kim tra vin placebo
Kt qu:

51

Mu th

Haginat 500

Pmz-Zanimex
250

Cerzinate 250

Ln

Nng

Nng

Hm lng

Cefuroxime

Cefuroxime

cefuroxime

axetil trong

axetil trong

axetil trong

vin placebo

vin m

vin placebo

(%)

hnh

so vi vin m

(%)

hnh

0.00

66.39

(%)
0.0

0.00

65.98

0.0

0.00

66.12

0.0

0.00

0.00

63.21

0.0

0.00

62.98

0.0

0.00

62.01

0.0

0.00

61.97

0.0

0.00

62.13

0.0

63.44

0.0

Thc nghim: Kim tra cc vin m hnh c hm lng thay i xung

quanh hm lng vin thc t xy dng c.
Kt qu ( Ph lc ):
Haginat 500
Trong bao nhiu ln o

Min

Max

Nng
trung bnh
(%)

50.03

49.05

51.23

50.20

100.3

1.24

60.23

58.58

61.24

59.99

99.6

1.23

Nng
xy dng

Nng o c (%)

T l %
thu hi

%RSD

52

70.03

68.76

71.38

70.25

100.3

1.07

79.81

78.85

80.47

79.64

99.8

0.64

89.96

88.86

91.10

89.98

100.0

0.62

Bng 3.11: Kt qu thm nh ng ca phng php ng vi cng thc

Haginat 500

Nhn xt: T l % thu hi t .... nm trong khong 98,0%

102,0% v RSD < 2% => Phng php nh lng t yu cu
v ng.
Pmz- Zanimex 250

Min

Max

44.98

43.90

45.73

Nng
trung bnh
(%)
44.86

54.97

54.34

56.15

55.21

100.44

0.77

64.69

64.42

65.30

64.85

100.25

0.39

74.83

73.79

75.00

74.37

99.38

0.47

84.79

84.47

85.45

84.97

100.21

0.27

Nng
xy dng

Nng o c (%)

T l %
thu hi

%RSD

99.73

1.07

Bng 3.12: Kt qu thm nh ng ca phng php ng vi cng thc

Pmz-Zanimex 250

Nhn xt: T l % thu hi nm trong khong 98,0% 102,0% v

RSD < 2% => Phng php nh lng t yu cu v ng.
Cerzinate 250
Nng

Nng o c (%)

Nng

T l %

53

xy dng

Min

Max

40.4

39.85

41.19

trung bnh
(%)
40.42

49.93

49.35

50.64

60.26

59.61

69.58
79.84

thu hi

%RSD

100.06

0.92

49.92

99.98

0.73

61.00

60.22

99.93

0.60

69.17

70.28

69.65

100.11

0.35

78.92

80.93

79.79

99.94

0.63

Bng 3.13: Kt qu thm nh ng ca phng php ng vi cng thc

Cerzinate 250

Nhn xt: T l % thu hi nm trong khong 98,0% 102,0% v

% RSD < 2% => Phng php nh lng t yu cu v
ng.
3.3.4. lp li
Kt qu:
Haginat 500
Hm lng
Ln o

Cefuroxime axetil o c Trung bnh

(%)
66.47

2
3
4
5
6

65.91
67.07
67.37
66.26
66.63

% RSD

(%)

66.6

0.5

Bng 3.14: Kt qu thm nh lp li ca phng php ng vi cng thc

Haginate 500

54

Nhn xt: % RSD < 2 % => Phng php nh lng t yu cu v

lp li.
Pmz- Zanimex 250
Hm lng
Ln o

Cefuroxime axetil

Trung bnh

(%)

(%)

63.02

2
3
4
5
6

62.88
62.54
63.88
63.44
63.48

63.2

% RSD

0.5

Bng 3.15: Kt qu thm nh lp li ca phng php ng vi cng thc

Pmz- Zanimex 250

Nhn xt: % RSD < 2 % => Phng php nh lng t yu cu v

lp li.
Cerzinate 250
Hm lng
Ln o

Cefuroxime axetil

Trung bnh % RSD

(%)

(%)

63.31

2
3
4
5
6

63.43
63.46
64.00
63.46
63.24

63.5

63.5

55

Bng 3.16: Kt qu thm nh lp li ca phng php ng vi cng thc

Cerzinate 250

Nhn xt: % RSD < 2 % => Phng php nh lng t yu cu v

lp li.
3.3.4.1. chnh xc trung gian
Thc nghm: Tin hnh trong cng mt phng th nghim nhng bi 2
kim nghim vin khc nhau v hai ngy phn tch khc nhau. Xc
nh gi tr % RSD kt qu nh lng gia hai ln th nghim.
Kt qu:
Haginat 500
S ln o

Kim nghim vin 1

Kim nghim vin 2

66.47

66.06

65.91

66.46

67.07

67.52

67.37

67.12

66.26

66.61

66.63

66.91

Gi tr trung bnh

66.70

% RSD

0.75

Bng 3.17: Kt qu thm nh chnh xc trung gian ca phng php ng

vi cng thc Haginate 500

Nhn xt: % RSD < 3 % => Phng php nh lng t yu cu v

chnh xc trung gian
Pmz-zanimex 250

56

S ln o

Kim nghim vin 1

Kim nghim vin 2

63.02

63.79

62.88

62.30

62.54

62.36

63.88

62.81

63.44

62.78

63.48

62.79

Gi tr trung bnh

63.01

% RSD

0.84

Bng 3.18: Kt qu thm nh chnh xc trung gian ca phng php ng

vi cng thc Pmz-Zanimex 250

Nhn xt: % RSD < 3 % => Phng php nh lng t yu cu v

chnh xc trung gian
Cerzinate 250
S ln o

Kim nghim vin 1

Kim nghim vin 2

63.31

62.77

63.43

62.84

63.46

63.81

64.00

62.43

63.46

62.41

63.24

63.27

Gi tr trung bnh

63.20

% RSD

0.79

57

Bng 3.19: Kt qu thm nh chnh xc trung gian ca phng php ng

vi cng thc Cerzinate 250

Nhn xt: % RSD < 3 % => Phng php nh lng t yu cu v

chnh xc trung gian.
3.4. ng dng phn tch thuc trn th trng
S dng ng tuyn tnh nh lng cc mu th
Cc mu thuc c bc lp v bao v qut trc tip ph NIR ca tng
vin. Mi mu thuc c phn tch ba ln bng 5 ln qut trong 1 ln
thu ph vi phn gii 12 cm-1 trong phm vi ca 6250 cm-1 -4167
cm-1 v loi b ph nn ca mi trng phng. S dng ng tuyn
tnh NIR ca vin nn tng ng cho nh lng.
Cng thc tnh hm lng (%) ca Cefuroxime axetil:

X (%)=

C xW
1000 x P

x814.5

C: Hm lng ca cefuroxime axetil trong mu (%).

W: Khi lng trung bnh ca vin nn (mg)
P: Hm lng cefuroxime ghi trn nhn (mg)
814.5 g /mg: Hm lng chun C16H16N4O8S (g) trong 1mg nguyn liu ,
tnh theo ch phm nguyn trng
Kt qu phn tch thuc:
Haginat 500

58

Hm lng Khi

Ln Hm lng

Trung %

cefuroxime lng

(%)

bnh

Cefuroxime

ghi trn

trung

axetil o

nhn

bnh vin

(mg)

(mg)

(%)

500

941.1

66.47

2
3
4
5
6

65.91
67.07
67.37
66.26
66.63

RSD

(%)

101.9
101.0
102.8
103.3
101.6
102.1

102.1

0.78

Bng 3.20: Kt qu phn tch thuc Haginate 500

Pmz- Zanimex 250
Hm lng Khi

Ln o

Hm

cefuroxime lng

lng

ghi trn

trung

Cefuroxi

nhn

bnh vin

me axetil

(mg)

(%)

250

495.6

X (%) Trung
bnh

63.02

101.9

2
3
4
5
6

62.88
62.54
63.88
63.44
63.48

101.0
102.8
103.3
101.6
102.1

102.0

Bng 3.21: Kt qu phn tch thuc Pmz-Zanimex 250

Cerzinate 250

%
RSD

0.78

59

Hm lng Khi

Ln

Hm lng

Trung

cefuroxime lng

Cefuroxime

(%)

bnh

RSD

ghi trn

trung

axetil

nhn

bnh vin

(%)

(mg)

(mg)

250

503.6

(%)

63.31

103.9

2
3
4
5
6

63.43
63.46
64.00
63.46
63.24

104.1
104.1
105.0
104.1
103.8

104.2

Bng 3.22: Kt qu phn tch thuc Cerzinate 250

0.38

Kt lun:
T mc tiu ra, kha lun thu c cc kt qu sau:
xy dng c 3 cng thc v ch to cc vin nn m hnh cha
Cefuroxime axetil trn 3 nn t dc c trng c hm lng da trn
thnh phn cng b ca cc mu thuc Haginat 500, Pmz-Zanimex
250, Cerzinate 250.
T cc hm lng cefroxime axetil thay i xung quanh hm lng
vin thc t xy dng thit lp c ng tuyn tnh bc mt vi
h s tuyn tnh R > 0,99.
nh lng c hm lng cefuroxime trong 3 mu th Haginat
500, Pmz-Zanimex 250, Cerzinate 250.
thm nh c quy trnh phn tch bao gm cc ch tiu: tuyn
tnh, c hiu , ng, lp li, chnh xc trung gian. Kt qu
cho thy phng php t yu cu v tuyn tnh, c hiu ,
ng, lp li, chnh xc trung gian.
Qua nhiu nghin cu, k thut NIR chng minh c y l mt k
thut phn tch nhanh, dng c nh tnh, nh lng v sng lc
nhanh thuc gi v thuc km cht lng; tit kim c thi gian, ha
cht cng nh chi ph. T cc kt qu kha lun thu c c th khng
nh phng php quang ph cn hng ngoi c th c ng dng
nh lng nhanh cc vin nn cha cefuroxime axetil
Qua kt qu ca kha lun, mong rng chng ta tip tc kho st trn
nhiu i tng thuc cha cefuroxime axetil hn na khng nh
tnh ng n ca phng php, ngoi ra chng ta cn nghin cu v
pht trin phng php NIR trong phn tch nhiu loi hot cht v cc
dng bo ch khc na

TI LIU THAM KHO:

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PH LC
Cng thc vin Haginate
500
Nng Nng o
xy dng
c
50.03
50.85

Cng thc vin PmzZanimex 250

Nng
Nng
xy dng
o c
44.98
45.69

Cng thc vin

Cerzinate 250
Nng
Nng
xy dng
o c
40.40
40.39

50.03

51.19

44.98

45.57

40.40

40.11

50.03

51.23

44.98

45.73

40.40

40.21

50.03

50.11

44.98

44.84

40.40

41.00

50.03

50.41

44.98

44.56

40.40

41.19

50.03

49.59

44.98

44.82

40.40

40.24

50.03

50.24

44.98

44.91

40.40

40.65

50.03

49.76

44.98

45.02

40.40

40.64

50.03

51.21

44.98

45.24

40.40

40.25

50.03

50.20

44.98

45.35

40.40

40.38

50.03

49.98

44.98

44.56

40.40

39.98

50.03

50.50

44.98

45.24

40.40

40.58

50.03

49.37

44.98

44.65

40.40

40.36

50.03

49.62

44.98

43.90

40.40

40.08

50.03

50.53

44.98

45.02

40.40

40.38

50.03

50.60

44.98

44.33

40.40

40.98

50.03

51.01

44.98

45.11

40.40

41.15

50.03

49.63

44.98

44.81

40.40

40.84

50.03

49.70

44.98

44.75

40.40

39.99

50.03

49.88

44.98

45.24

40.40

40.11

50.03

50.63

44.98

44.49

40.40

40.44

50.03

50.06

44.98

44.32

40.40

40.17

50.03

49.05

44.98

44.84

40.40

40.42

50.03

49.47

44.98

44.04

40.40

40.25

60.23

60.02

44.98

44.40

40.40

39.85

60.23

60.50

54.97

55.29

49.93

49.76

60.23

60.40

54.97

55.34

49.93

49.35

60.23

60.02

54.97

55.38

49.93

49.80

60.23

61.24

54.97

55.53

49.93

50.64

60.23

60.11

54.97

56.15

49.93

50.51

60.23

60.00

54.97

54.40

49.93

49.80

60.23

60.05

54.97

54.67

49.93

49.57

60.23

58.70

54.97

55.22

49.93

49.49

60.23

58.61

54.97

54.86

49.93

50.16

60.23

59.94

54.97

55.53

49.93

50.18

60.23

60.75

54.97

55.08

49.93

49.58

60.23

60.41

54.97

55.64

49.93

49.64

60.23

60.11

54.97

55.65

49.93

49.61

60.23

60.58

54.97

55.46

49.93

50.37

60.23

58.78

54.97

55.18

49.93

50.23

60.23

59.64

54.97

54.94

49.93

49.87

60.23

59.64

54.97

55.00

49.93

49.72

60.23

59.01

54.97

54.83

49.93

49.71

60.23

58.58

54.97

55.16

49.93

50.59

60.23

60.34

54.97

54.34

49.93

50.28

60.23

60.31

54.97

55.71

49.93

49.84

60.23

60.84

54.97

55.60

49.93

49.51

60.23

60.67

54.97

55.43

49.93

49.76

60.23

60.53

54.97

55.20

49.93

49.94

70.03

68.76

54.97

54.76

49.93

50.15

70.03

69.11

64.69

65.30

60.26

60.28

70.03

69.06

64.69

64.98

60.26

60.09

70.03

69.96

64.69

65.10

60.26

60.09

70.03

70.61

64.69

65.14

60.26

60.63

70.03

70.64

64.69

64.93

60.26

60.42

70.03

70.85

64.69

64.42

60.26

60.53

70.03

71.38

64.69

64.65

60.26

60.06

70.03

70.53

64.69

64.77

60.26

60.38

70.03

70.96

64.69

64.77

60.26

60.60

70.03

69.43

64.69

65.11

60.26

61.00

70.03

69.79

64.69

64.43

60.26

59.73

70.03

69.51

64.69

65.24

60.26

59.92

70.03

70.40

64.69

64.98

60.26

59.61

70.03

70.76

64.69

65.02

60.26

60.27

70.03

70.68

64.69

64.75

60.26

59.75

70.03

70.49

64.69

64.64

60.26

60.29

70.03

70.68

64.69

64.99

60.26

60.63

70.03

70.54

64.69

64.75

60.26

60.75

70.03

71.28

64.69

64.49

60.26

60.10

70.03

69.35

64.69

64.71

60.26

60.12

70.03

69.20

64.69

64.54

60.26

59.84

70.03

70.63

64.69

65.12

60.26

59.78

70.03

70.75

64.69

64.76

60.26

59.84

70.03

70.91

64.69

65.04

60.26

60.56

79.81

79.59

64.69

64.64

60.26

60.24

79.81

79.57

74.83

74.18

69.58

69.51

79.81

80.44

74.83

73.79

69.58

69.17

79.81

78.85

74.83

74.27

69.58

69.36

79.81

79.54

74.83

74.84

69.58

69.57

79.81

79.73

74.83

73.98

69.58

69.46

79.81

79.67

74.83

74.82

69.58

69.78

79.81

78.99

74.83

75.00

69.58

69.48

79.81

79.08

74.83

74.62

69.58

69.55

79.81

79.77

74.83

74.55

69.58

69.57

79.81

79.84

74.83

74.44

69.58

69.74

79.81

80.47

74.83

74.15

69.58

69.58

79.81

80.29

74.83

74.72

69.58

69.67

79.81

78.90

74.83

74.50

69.58

69.46

79.81

79.16

74.83

73.82

69.58

69.46

79.81

80.23

74.83

73.98

69.58

69.61

79.81

80.32

74.83

74.13

69.58

70.28

79.81

80.04

74.83

74.34

69.58

69.74

79.81

79.38

74.83

74.65

69.58

70.07

79.81

79.10

74.83

74.73

69.58

69.70

79.81

79.28

74.83

74.85

69.58

69.87

79.81

78.94

74.83

74.45

69.58

70.11

79.81

79.97

74.83

74.26

69.58

69.74

79.81

79.86

74.83

74.04

69.58

69.61

79.81

80.06

74.83

74.22

69.58

69.47

89.96

89.68

74.83

73.86

69.58

69.78

89.96

89.27

84.79

84.47

79.84

80.93

89.96

89.53

84.79

85.00

79.84

80.41

89.96

90.93

84.79

85.45

79.84

80.21

89.96

90.15

84.79

84.96

79.84

80.17

89.96

90.03

84.79

84.81

79.84

79.91

89.96

89.76

84.79

85.04

79.84

79.70

89.96

91.10

84.79

84.69

79.84

79.12

89.96

90.01

84.79

84.66

79.84

79.27

89.96

90.35

84.79

84.84

79.84

79.60

89.96

90.29

84.79

84.75

79.84

79.31

89.96

90.02

84.79

85.13

79.84

80.12

89.96

90.65

84.79

85.10

79.84

80.16

89.96

89.39

84.79

85.00

79.84

79.50

89.96

89.91

84.79

84.95

79.84

79.89

89.96

88.86

84.79

85.31

79.84

80.39

89.96

89.82

84.79

84.73

79.84

79.18

89.96

90.16

84.79

84.88

79.84

79.23

89.96

89.08

84.79

85.09

79.84

79.09

89.96

90.70

84.79

85.21

79.84

78.92

89.96

90.44

84.79

85.30

79.84

79.78

89.96

90.04

84.79

84.74

79.84

80.33

89.96

90.23

84.79

79.84

80.02

89.96

89.77

84.79

85.01

79.84

79.81

89.96

89.38

84.79

85.02

79.84

79.95

84.97