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Nghien CCFU - Ky thuat

Tong quan iing dung quang pho dao ham trong dinh lu-ong thuoc da thanh phan Phan 2: Cac phwang phap dinh luffng hon hop

da thanh phan bang quang pho dao ham

Nguyin Phirong Nhung, Vu Ddng Ho^ng*

Sp mon Hoa Phdn tich vd Doc chdt - Truang Dcii hgc Dugrc Hd Noi

E-mail: [email protected] (Tiip theo so 442, thing 02/2013)

Summary

Various algorithms are of common use in derivative UV-Vis spectrophotometry for quantitative analysis were reviewed. The recent and current developments, occurring limitations of the derivative spectrophotometry for drug analysis In Vietnam were discussed.

Keywords: Derivative UV-Vis spectrophotometry, quantitative analysis, different algorithms.

Cac phipang phap djnh lipp'ng hon phoang phdp ndy phi dgo hdm dope sd dgng hffp da thanh ph^n bang quang pho khodng ed bde m|t hogc hai (hlnh 1).

d^o ham

VI phi dgo hdm la kit qua cda phdp biin d&' td phi hip thg nen gia tri cda phi dgo hdm tgi ede bode song edng cd so cdng tinh nho pho hip thu eCia dung djch c6 nhieu thdnh phan vdi dieu kidn toang tdc gida cac thanh phin ndy Id khdng ddng k l vd cd t h i bo qua:

A = (eiQ + €202 + ... + £kC0l (1)

-(if^

de.

^^.) (2)

E

t

Q -0.100

3 " 3 •

r y^^\ .271.8 nm

1

^265.6 ™n\«V , ^ ^

Trong do: e, va C, lan I o 0 Id d | hip thu phdn td vd ning d6 cda thdnh phan % trong dung djeh CO k thdnh phin (1 < i < k).

Phoo'ng phdp dgo ham giao dilm khong (Zero<ro5sing Derivative Spectrophotometry)

Day la phoang phdp doyc sd dgng pho bien nhat trong vigc dng dgng quang pho dgo ham de djnh lop'ng dong thdi hon hap hai thanh phan.

Phoang phdp ndy dya tren nguydn tae bode song dop'c lya chpn la bode song tgi d6 dgo ham dp hip thu cda mpt trong hai thdnh phin d n dinh lop'ng t}ang 0 vd thdnh phan eon Igi khac 0. Vdi

Bi/dc s6ng (nm)

Hinh 1: Dgo him b$c 1 cOa lamivudin (1) 15 pg/ml; (2) 20 pg/ml; (3) 30 pg/ml (dwang nit liin) va zidovudin (1) 30 pg/ml; (2) 50 pg/ml; (3) 75 pg/ml (dwdng net ddi) trong methanol. MQi tin chibwac sdng djnh /uprig'^^'

Niu hon hpp cd ba ttianh phin, [rfioang phdp nay ddi hdi phdi tim dop-c m^t bode sdng d l dgo hdm dp hap thg cOa d hai trong ba thanh phin bang 0 vd thdnh phan c&i Igi khdc 0. Cdng vide ndy khong phdi ICic ndo cung thyc hign dope Vi vgy, khi djnh lop'ng ba thdnh phin ngodi ta thodng dp dgng phoang phdp dgo hdm t^ dii.

T ^ CHi DlTQC HQC - 05/2013 (S6 445 NAM 53)

(2)

' Nghien ci>u - Ky thugt

Phuvng phdp d^o ham pho ty dil (Ratio Spectra Derivative Spectrophotometry)

D90 ham ph6 t^ dii giao nhau t^i diim khdng (Zero-crossing raUo spectra derivative spectrophotometry)

Xdt dung dich ed hai thdnh phin Si, S2 va cd tinh chit cpng tfnh dnh sdng.

Khi do phoang trinh (1) trd thdnh:

A = (SiCl + £2C2)I (3) Chia phi hip thg eua dung djch cho pho hap thg eua dung djch chuin Si co nong dd Q ^^ ta dope pho ty doi:

Dgo hdm hai v l cda phoang trinh (4):

d\ A -\ d [ Cl e; C2 ] Q,<^p2]C2_d feji Cg dXlA^rdxlc^s, eiC9.sJ~ dAUjCt^ dAUjc^j

(4)

(5) Tgi mpt bode sdng xae ^nh, phi dgo ham ty

dil ehl phg thupc vdo nong dp cda chit 82 va ning dp eda dung djeh chuin Si. VI ning dd cua dung djch ehuIn Si da bilt ndn cd the xac

djnh dope ning d | eda chit 82 trong dung djch tgi mpt bode sdng doac loa chpn thich hpp (tin higu dgo hdm c6 gid tn khac 0) (hinh 2).

Bif6c (Ang (nm)

Hinh 2: (a) Phi t^ dii cua acetaminophen tai cic ning dd (a) 5,0 pg/ml, (b) 17,5 pg/ml, (c) 25,0 pg/ml, (d) 37,5 pg/ml, (e) 50,0 pg/ml khi ning dd cOa si chia (mephenoxalon) li 12,5 pg/ml trong methanol (M = 4 nm). (b) Pho dao him fj? dii bic 1 cOa acetaminophen t^i cic nong d^ (a) 5,0 pg/ml, (b) 17.5 pg/ml, (c) 25,0 pg/ml, (d) 37,5 pg/ml, (e) 50,0 pg/ml khi ning d^ cOa si chia (mephenoxalon)

J15}

li 12,5 pg/ml trong methanol (AA = 4nm^' v l ea ban, phoang phdp ndy ed thi dng dgng d l djnh lopng ba thanh phin trong hln hap- Lly pho hip thg eua dung djeh cd ba thanh

phan 81. $2 vd S3 chia cho phd hip thu cda dung djch chuan m|t trong ba chit, gid sd Id Si:

(CiCi + eiCz + eaC^jt C^ Ca C, c, Cg

Dgo hdm pho ty' dil, ta dope:

d [ ^ 1 ^ d r Cl e, C2 Ca C3 1 d real C; d Uji

•HSi,

(6)

(7) Khdc vdi djnh lop'ng hai thanh phin ehl d n thdnh phin bode sdng thich hpp Id bode sdng md lya chpn mOt bode sdng sao cho tin hidu dgo ham phi ty doi cCia chit Si vdi dung djch chuan Si c6 phi ty dii du Idn vd dam bao tinh tuyln tinh dgo hdm bang 0 edn dgo hdm cCia pho ty dot cda (thodng Id bode sdng eye dgi), d l djnh lopng ba 82 vdi dung djch chuin Si khdc 0 (hinh 3).

TJ^V CHi DlTQC HQC - 05/2013 (S6 445 N A M 53)

(3)

• Nghien CCFU - Ky thuat

cua hai thanh phan S, vS S2 co nong dp lan ]U!r[

la ^o,S| '-'0,52 •

E3C,

*I>S.S, ' i C o j , + '2'^OJi ^l*-"^ + '2'i"> (8)

Tai m6t vung bu-dc s6ng hoac mot so blrdc song nhit djnh, so hang t h * nhat trong phu'ong trinh (8) i<h6ng d6i, do 36 khi lay dao h^m:

Hinh 3: Ph6 tfao ham ty d6i bac 1 cua acid acetylsallcyllc (ACA): (a,) 8 iig/ml; (b,j 12 isglml;

(C) 16 ijg/ml; (d,j 20 ijg/ml; (e,) 24 fjg/ml: va cua acid ascorbic (ASCA) (aj 8 fjg/mt: (bJ 12 Ijg/ml; (cj 16 jig/ml; (di) 20 ijg/ml; (ei) 24 iig/mi (16 iig/ml paracetamol (PAR) la so chia) trong methanol va HO 0,2M (1:3; f M = 8 nmf^

Dao ham ph6 ty doi so chia kep (Double divisor ratio spectra derivative spectrophotometry)

Phu-ong phdp nay du'g'c sCr dyng de djnh iyong dung djch ba thanh phan. d dSy, dung dich chuin Si duoc thay bang dung djch chuan

dX\A,

Khi '^OA trd thanh:

f A 1 ^ d I e,C. 1

(9)

' ^ O A ~ ^ » , phu'O'ng trinh (9)

dX\A.

[ A 1 ^ d f £3 1 Ci

\.Aas,s,\ iAci + Cti'Ct (10) Phu'ong trinh (10) cho thiy tin hieu ph6 a?o hSm t j doi i<h6ng phu thuoc vao n6ng dp cua Si va Sa trong mlu thCr. Cdc buo'c sdng md tai 36 tin hi#u pho dao ham CLPC dai hay ci^o tiiu thudng du-pc lu'a chpn d l djnh lupng th^nii phin S3 (hinh 4).

%

1 1

i

•i

• • !

%\%

241 Join

/ .

1

267.4 nm

BuOc MSng (nm)

Hinh 4: So trung l$p ciJa phi d?o him t'^ ddi bic 1 cOa: (a^) 16 pg/ml acid acetylsalicylic nguyin chit va hdn hgp 16 pg/ml acid acetylsalicylic, 16 pg/ml acid ascorbic vi 12 pg/ml paracetamd (28 pg/ml paracetamol + 28 pg/ml acid ascorbic lam s6 chia); (bi) 16 pg paracetamol nguyen chit vi (b^

hon hgp 16 pg/ml paracetamol, 16 pg/ml acid acetylsalicylic vi 16 pg/ml acid ascorbic (12 pg/ml add acetylsalicylic + 12 pg/ml acid ascorbic la so chia); (ci) 12 pg/ml acid ascorbic nguyin chit vi (c^ h6n hgp 12 pg/ml add ascorbic. 16 acid acetylsalicylic vi 12 pg/ml paracetamol (20 pg/ml acid acetyl salicylic + 20 pg/ml paracetamol li si chia) trong methanol va HCI 0.2M (1: 3)'^'*^

Dao ham phi ty doi lien tyc (Successive ratio spectra derivative ^ectrophotometry)

D6 hip thg eua dung dieh ba thdnh phin Si,

Sz, S3:

A = (siCi + EiCi + €30^1 (11)

Chia d hai v l cua phoang trinh (11) cho

phi hip thg eda mpt dung djeh ehuan cda Sii

T ^ CHi DlTQC HQC - 05/2013 (S6 445 N A M ^

(4)

• Nghien cipu - Ky thuat

(12)

" 0 ^ Cji-o,:^ *-OJi

Khi lly dgo hdm bgc 1 Uieo bode sdng, phoang trinh (12) trd thanh:

d A d r ciCi 1 d r EaC21

dA^oj. " dX UtCo^l dX U c o ^ l - (^3)

Ldp Igl phdp chia vd lly dgo hdm d trdn nhong thay so chia bang I Au/l '^^ai (toang dng vdi pho dgo ham ty doi bde 1 cua dung djch ehuIn gom hai chit S2va S3), kit qua euol eung thu dop'c:

dx[dXAoJ~ dXLd 1

i(^h

OS,

(14)

Trong phoang trinh (14), dgo hdm pho ty dii lien tgc t^ Id vdi ning dd eda Si va khong phg thu$c vdo ning d0 cda hai chit con Igi trong hln hpp. Do do, bdng phoang phdp nay c6 thi djnh lopng Si trong hln hdP ba thanh phin (hlnh 5).

1.4 g. 1.2

•a 1- J ' 0.8 S "

0.4 OS ' N

A : ^ ^

600 eSO 700 BuSc s6iig (nm)

-M-

560 ! IB 570 575 5 0

(b) BiAlc sdng (nm)

Hinh 5: Phi hip thij cCia ph(rc Zn^* (ning dl? 0,1, 0,5, 1,0 va 1,5 pg.mf^) v&i 1-(2- pyridylazo)-2-naphthol (5.1(f moi.f') tai pH 9,2 trong mdi trwong mixen (a) vi phi dao him b$c 1 cua phi ty dil thw hai vdi A/i=1 nm (b) theo phwang trinh (14f^^

TAP CHi DlTQC HQC - 05/2013 (S6 445 NAM 53)

Tmh hlnh nghien CLPU trong niFd'C 6 Viet Nam, so lopng cdc edng trinh nghien cdu dng dgng pho dgo ham con rat han chi niu so vdi so cdc cdng trinh dope cdng bitren the gidi dope thing ke cho tdi na/^^^^' ^°'^^'. Bdng 1 thong ke ede cdng trinh d\xqic cdng b l d hai tgp chf Kiem nghidm thule va Dope hpc trOng giai dogn 1990 cho tdi nay (xem trang sau). Da s l cdc nghidn cdu sd dgng phi dao ham bgc nhlt'^' ^- •*• ^- ^' ^^' va dgo ham bae nhat pho ty g^][3,7,12] ^1 ^^^^ lu'gng ede che pham hai thanh phan. Co the nhdn thdy, djnh lopng bang quang pho dgo hdm diu co qui trinh xd ly miu dan gian, sd dung dung moi thdn thien vdi mdi trodng, tilt kigm chi phi vd thdi gian, cd dfi dung vd dp lap Igi eao. Tuy nhidn, phi d l va trinh ty toi ou hoa phep lay dgo hdm dope trinh bay trong cdc bdi bdo ndy eon kha dan gidn.

Vigc kiem tra sy eOng tinh eua anh sdng trong vung bode sdng khao sat va anh hodng eda ta dop'c (so sdnh phi hdp thg cua chit chuin vd ehl phim d edng nong dp) choa thyc sy doac ehd trpng. Khac vdi phan Idn ede nghien edu tren thi gidi, so sdnh dd ddng va dp Igp eda phep djnh lopng bdng quang pho vd HPLC bang thong ke todn hpc chf dop'c friye hidn d mpt s6 nghien cdu'^ ^. Ddng chd y, cac nghidn cdu trong node hodn todn choa khai thde dope nhdng phdn mem xd ly tin hidu tidn tiln eho phep lay dgo ham va ldm tran pho. Day co the la mpt trong nhdng ly do han ehl vigc dng dgng phi dgo hdm trong cdng tde kiem nghiem thuoc hign nay.

Ket luan

Tom Igi, tong quan v l cTinh loang cae ehl pham da thdnh phan bdng quang pho dgo ham eho thiy mpt so dilm ddng chu y nho sau:

- Do pho hap thg c6 tinh chit toang ty vdi hdm phan b l Gauss ndn trdn phi dgo hdm se xuit hign ede pic mdi Idm tdng kha ndng phdn tich pho hap thg ban diu.

- Cdc ky thudt dinh lopng bang quang phi dgo ham ngay eang cd tinh kha thi cung vdi sy ra ddi cda cac mdy quang phi vd phan mem xd lytln hidu hidn dgi.

Do vgy, dng dgng quang phi dao hdm tgi

cdc phdng thf nghidm dop'c trang bi cdc mdy do

quang hign dgi se gop phan giam thilu sy phu

thupc vao phoang phdp sic ky trong edng tdc

kilm nghiem thodng quy.

(5)

• Nghien ciJu - Ky thugt

L d i c a m a n

Tong quan nay dwac thwc hiin trong di tii so 104.07-2012.58 do Quy phit triin khoa hoc

B a n g 1 : lyng di^ng quang phi d^o him & Viet Nam tie nim 1990dinnay

va cong nghi quoc gia Viet Nam (NAFOSTED) tai tra.

Hap chit

Acid benzoic (Be) vd acid salicylic (Sc) Cafein va natrl benzoat

Cloramphenicol (0) va Naphazolin (N)

Cloramphenicol (C), Naphazolin nltrat (N) va Dexamethason natriphosphat (D) Loratadin (L) va Pseudoephedrin sulfat (P) Loratadin (L) va Pseudoephedrin sulfat (P)

Nimesulid

Papaverin (P) vd Theophylin (T)

Quinin hydnsclorid

Sulfadoxin (S), Pyrimethamin (P)

Sulfamethoxazol (S) va Trimethoprim (T) Vitamin B l va vitamin B6

Dung mdl H2O

H2O

H2O

HCI 0,1 N

HGi 0,1N

Ethanol

HCI 0,IN

HC! 0,1 N

HG!0,1N

NaOH 0,1N HCI 0,1N

f Dac diem P h i dgo ham bde 2 tgi 282,7 (Be) vd 322 nm (Sc); trong thulc md P h i dgo ham t^ d ^ bgc 2 tai 220 nm (natri benzoat) va 226 nm (cafein) trong thulc tiem.

Pho dao hdm ty doi bac 1 tgi 282,93 (C)vd 226,12 nm(N);

trong thuoc nh6 mat

P h i dao hdm ty ddi bac 1 tgi 218,6 (C), 223,4 (D) va 239,4 nm (N);

trong thuoc nho mat

P h i dao hdm bac 1 tai 306,7 (L) vd 261,8 nm (P); trong vien ndn Dao hdm bde 1 tgi 261,2 (P) vd 306,6 nm (L);

trong nguyen lieu va vien nen P h i dgo ham bac 2 tai 260 nm;

trong vien nen

Pho dgo ham bac 1 tai 250,8 (T) va 243,7 nm (P); bgc 2 tgi 287,2 (T) va 257,6 nm (P); trong vien nen P h i dgo ham bgc 1 tgi 257,7 nm;

cd mgt s i n pham phan hdy Pho dgo ham bgc 1 (1) tgi 240,5 (P) va 262,3, 271,8 nm(S);

trong vidn ndn

Dgo hdm ty doi bac 1 tai 251 (S) vd 245 nm (T) trong vien nen

P h i dao hdm bde 1 (1) tai 254, 290,6 (81); 226,5 vd 247,2 nm (86), p h i dao hdm bgc 2 (2) tgi 228,6, 239,2 (81) vd

258,0 nm (B6); trong vien nang

Khoang tuyin tfnh 59,40-139,9 (Be), 30 - 90 |jg/ml (Sc) 2 . 7 5 - 3 0 (natri

benzoat), « 2.5 - 20 (cafein) pg/m!

0 , 6 - 1 , 4 ( 0 ) , 0 , 3 - 0 , 7 ( N ) m g %

8 - 6 4 ( C ) , 2 - 1 6 ( D ) v d 1 - 8 ( N ) p g / m l

5 - 5 0 ( L ) , 1 8 0 - 1 0 0 0 (P) pg/ml 0,015-0,035 mg/ml (L), 0,36-0,84 mg/ml (P)

1 - 1 0 0 ^Jg/ml

0,7 - 6,3 (P), 3,0-9.0 (T) pg/ml

1 5 - 3 5 pg/ml

( 1 ) 2 - 4 ( P ) . 4 0 - 8 0 (S); (2) 7 , 5 - 4 5 (P), 1 5 0 - 9 0 0 ( 3 ) pg/ml 1 0 - 6 0 ( S ) , 2 - 12 (T) pg/ml 2 , 5 - 4 0 ^Jg/ml(B1, 86)

TLTK [8]

[9]

[3] '

l!

m

[1]

[11]

[101

[4]

[2]

[51

(12)

[6]

Tai li|u tham khao

1. Dmh Thj Hdi Binh, Ld Thj Ngoc Didp, Nguyen Thanh Hai vS Trjnh Van L i u (2010), "Djnh lopng dong thdi loratadin va pseudoephedrin bang phoang phap quang p h i dgo ham bde n h i f , T^p c^i Kiem nghiem thuoc s l 2, trang 1 3 - 1 7 .

2. Ngd Tuan Cpng va To Minh Hung (1997),

"Phoang phdp quang pho dao ham djnh lopng nhanh quinin hydroclorid khi c6 l i n chit phdn huy", Thong bao Kiem nghidm so 2, trang 23 - 28.

3. Ngfi Tuin COng, Nguyin Thu Hoang vd Tfi Mmh Hung (1999), "SCK dung may tfnh l l y gid trj dgo

ham bgc 1 pho ty doi djnh lopng cloramphenicol va naphazolin trong thdnh phan thuoc Naphaxetin", T$p chi Kiem nghiim thudc s l 2, trang 1 1 - 1 6 .

4. Tran To Hieu, Bui Thj Hao, Trjnh Vdn QuJ vS Dang Tran Phoang H i n g (2003), "Djnh lopng fling thdi papaverin va theophylin trong thulc Sedokal bang phoang phdp quang p h i Ago hdm", T^p chi Kiim nghiim thuic so 2, trang 19 - 23.

5. Dgng Trln Phoang Hong vd Trjnh Vdn Qu?

(1997), "Djnh lopng dong thdi sulfadoxin vS pyrimethamin tn3ng vidn nen Fansida bdng phuong phdp HPLC vd phoang phdp quang p h i dgo h^m", Thing bio Kiim nghiim s6 1. trang 1 - 1 1 . TAP CHI DlTQC HQC - 05/2013 (S6 445 N A M ^ , ^

(6)

• Nghidn CCFU - Ky thuat

6. Dgng Trln Phoang Hong va Trjnh Van Quy (1996), "Djnh lu'png ding thdi vitamin 81 vd vitamin 86 trong vidn nang vitamin 81 + 86 bang phoang phap quang p h i dgo ham", Thong bio Kiim nghiim s l 1 , t r a n g 6 - 1 1 .

7. Ddng Trln Phoang Hing va Trjnh Van Quy' (1996), "Dinh lopng Cloramphenicol, dexamethason natri phosphat vd naphazolin nltrat trong thulc nho mat Collydexa bing phoang phdp quang p h i tCr ngoai dgo hdm ty doi". Thong tjao Kiem nghi$m s6 1, trang 2 - 9 .

8. Cao Thj Mai Phoang (1998), "Djnh lu'png dong tho'i acid benzoic va acid salicylic trong thuoc md benzosali bang phoang phdp quang pho Ago hdm", Thdng bio KiSm nghi$m so 2, trang 1 - 5.

9. Thai Nguyen Hung Thu (2007), "Dmh lopng tryc tilp dung djch nhilu thanh phin bing quang pho Ago hSm t j dii", T^p chi Dupc hoc so 8 (376), 35-38.

10. Nguyin Thj Mong Thuy va Nguyin Di>c Tuin (2003), "Djnh lopng nimesulid trong vldn nen bing phu-ang phdp quang pho dgo ham bde 2", T^p chi Duxjfc hqc s l 4, trang 16 - 1 8 .

11. Ld Minh Trf va Nguyin Ma Huy Thanh (2003),

"Dmh lupng ding thdi loratadin va Pseudoephedrin sulfat trong c h i phim vien nen bang phuang phdp quang p h i td ngogi dao ham". Tap chi DUK?C hgc s6 2, trang 28 - 30.

12. NguySn Tudng Vy va Do Ngoc Thanh (2003),

"Djnh lopng ding thai Sulfamethoxazol vd trimethoprim trong vidn nen Trasepton bdng phoang phdp quang phi dgo hdm t j d6i", T^p chi Dut?c hgc s l 12, trang 2 8 - 2 9 .

13. A. Afkhami and M. Bahram (2005), "Successive ratio-derivative spectra as a new spectrophotometric method lor the analysis of temary mixtures", Spectrnt^anicaAcla Part A 61, pp. 869-877.

14. E. Dine (1999). "The spectrophotometric multicomponent analysis of a temary mixture of acid

ascorbic, acetylsalicylic acid and paracetamol by the double divisor-ratio spectra derivative and ratio spectra- zero aossing methods", TalantaAQ. pp. 1145-1157.

15. A. Y. El-Sayed and N. A El-Salem (2005),

"Recent Developments of Derivative Spectrophotomeby and Their Analytical Applications", Analytical Sciences 21, pp. 595 - 614.

16. N. Erk (1999), "Application of denvative- differential UV spectrophotome^ and ratio derivative spectrophotometric detemiination of mephenoxalone and acetaminophen in combined tablet preparation", Journal of Pharmaceutical and Biomedical Analysis 21, pp. 4 2 9 - 4 3 7 .

17. J Karpinska (2004), "Derivative spectrophotometry - Recent applications and directions of developments", Talanta64. pp. 801-822.

18. C. B. Ojeda and F. S. Rojas (2004), "Recent developments in derivative ultraviolet/visible absorption spectrophotometry", Analytica Chimica Acta 5^S. pp. ^-24.

19. C. B. Ojeda, F. S. Rojas and J. M. C. Pavon (1995), "Recent developments in derivative ultravidet/visible absorption specb'ophotometery", Talanta 42, pp. 1195 - 1214.

20. S. A. Ozkan and B Usiu (2002),

"Determination of lamivudine and zidovudine in binary mixtures using first derivative spectrophotometric, first derivative of the ratio-spectra and high-performance liquid chromatography-UV methods", Analytica Chimica Acta 466. pp. 175-185.

21. F. S. Rojas and C. 8. Ojeda (2009). "Recent development in derivative ultraviolet/visible absorption spectrophotometry: 2004-2008 A review", Analytica Chimica Acta 635, pp. 22 - 44.

22. F. S. Rojas, B. Ojeda and J. M. v... Pavon (1988), "Derivative ultraviolet-\^sible region absorption spectrophotometry and its analytical applications", Talanta 35 (10), pp. 753 - 761.

K h a o s a t . . . (Tiip theo trang 21)

4. Chambers Henry F., et al. (2009),

"Aminoglycosides & Spectinomycin", Basic & Clinical Pharmacology, Katzung Bertram G. , The McGraw- Hill Companies, inc., New York.

5. HolfoixJ Nicholas H. G. (2009),

"Pharmacokinetics & Pharmacodynamics: Rational Dosing & the Time Course of Drug Action", Basic &

Clinical Phamiacology, Katzung Bertram G., The McGraw-Hill Companies. Inc., NewYork.

6. McEvoy Gerald K. (2011), "Aminoglycosides General Statement", AHFS Drug Information®, American Society of Health-System Pharmacists, Bethesda, Maryland 814.

7. Nestaas E., et al. (2005), "Aminoglycoside extended interval dosing in neonates is safe and

elfective: a meta-analysis". Arch. Dis. Child Fetal.

Neonatal. Ed. 90(4), pp. F294-300

8. Pham Thi Thuy Van (2011), "Evaluation of efticacy and safety of amikacin usage in ICU's patients: A prospective observational study", Proceeding of Seventh Indochina Conference on Pharmaceutical Sciences. 14 - 16 December 2011, Bangkok Thailand.

9. Touw D. J., et al. (2009), "Therapeutic drug monitoring of aminoglycosides in neonates", Clin.

Pharmacokinet. 48(2), pp, 71-88.

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T ^ CHi DlTQC HQC - 05/2013 (SO 445 NAM 53)

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