TOBRAMYCIN

Tobramycinum

C18H37N5O9 P.t.l: 467,5

Tobramycin l 4-O-(3-amino-3-deoxy--D-glucopyranosyl)-2-deoxy-6-O-(2,6-diamino-2,3-6-trideoxy--
D-ribo-hexopyranosyl)-L-streptamin, c iu ch t Streptomyces tenebrarius hoc bng cc
phng php khc, phi cha khng it hn 900 g C18H37N5O9 trong 1 mg, tinh theo ch phm khan.

Tnh cht
Bt trng hoc gn nh trng. D tan trong nc, rt kh tan trong ethanol 96 %.

nh tnh
A. Phng php sc k lp mng (Ph lc 5.4).
Bn mng: Silica gel G.
Dung mi trin khai: Methanol - amoniac - cloroform (60 : 30 : 25).
Dung dch th: Ha tan 30 mg ch phm trong nc v pha long thnh 5 ml vi cng dung mi.
Dung dch i chiu (1): Ha tan 30 mg tobramycin chun trong nc v pha long thnh 5 ml vi cng
dung mi.
Dung dch i chiu (2): Hn hp ng th tich cua dung dich th v dung dich i chiu (1).
Cch tin hnh: Chm ring bit 3 l mi dung dich ln bn mng. Trin khai sc k n khi
dung mi i c khong 3/4 chiu di bn mng. Ly bn mng ra, dung mi bay hi v
sy bn mng 105 oC trong 15 min. Ngay lp tc phun dung dich ninhydrin (TT) 1 % trong
hn hp dung mi 1-butanol - pyridin (100 : 1). Vt tobramycin c mu hng. Vt chinh trn sc
k cua dung dich th phi tng ng v vi tri so vi vt chinh trn sc k cua dung dich
i chiu (1). Dung dich i chiu (2) ch cho mt vt duy nht c vi tri tng ng vi vt chinh
trn trn sc k cua dung dich i chiu (1).
B. Trong mc inh lng, pic chinh trn sc k cua dung dich th phi c thi gian lu tng ng
vi thi gian lu cua pic chinh trn sc k cua dung dich chun.

pH
T 9,0 n 11,0 (Ph lc 6.2).
Ha tan 1,0 g ch phm trong 10 ml nc khng c carbon dioxyd (TT) o.

Tp cht lin quan

Phng php sc k lp mng (Ph lc 5.3).
Bn mng: Silica gel G.
Dung mi trin khai: Dung dch natri clorid 29,2 % - ethanol 96 % - nc (50 : 30 : 20).
Dung dch hypoclorit loang: Pha long 20 ml dung dch natri hypoclorit (TT) thnh 100 ml bng nc.

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Thuc th tinh b t - kali iodid: Ha tan 1,1 g kali iodid (TT) trong 60 ml nc, un si trong 15 min,
thm t t hn dich cua 1,5 g tinh b t (TT) trong 10 ml nc. Thm 25 ml nc v un si trong 10
min. ngui v pha long thnh 100 ml bng nc.
Dung dch th: Chuyn 50 mg ch phm vo binh inh mc 10 ml, thm 7 ml nc ha tan v iu
chnh n pH 5,5 0,4 bng dung dch acid sulfuric 0,5 M (TT). Thm nc n vach, trn u.
Dung dch i chiu: Pha long dung dich th bng nc thu c dung dich c nng 0,05
mg/ml.
Cch tin hnh: Chm ring bit 1 l cc dung dich trn ln bn mng. Trin khai sc k n khi dung
mi i c khong 3/4 chiu di bn mng. Ly bn mng ra, dung mi bay hi di lung khng
khi nng v sy bn mng 110 C trong 10 min. Phun ln bn mng ang nng dung dch hypoclorit
loang. Lm kh bn mng bng lung khng khi lanh n khi phn bn mng phun di vach
chm ch cho mu xanh lam nhat khi nh mt git thuc th tinh bt - kali iodid.
Tip tc phun bn mng bng thuc th tinh b t - kali iodid, cc vt c mu tia hi xanh xut hin
ngay. Bt ky vt ph no trn sc k thu c t dung dich th khng c c mu m hn mu
cua vt chinh trn sc k thu c t dung dich i chiu (1,0 %).

Nc
Khng c qu 8,0 % (Ph lc 10.3).
Dng 0,3 g ch phm.

Tro sulfat
Khng c qu 0,3 % (Ph lc 9.9; phng php 2).
Dng 1,0 g ch phm.

Ni c t vi khun
Khng c qu 2,00 EU/mg (Ph lc 13.2).
Nu ch phm dng sn xut thuc tim m trong quy trinh khng c giai oan tin hnh loai b ni
c t vi khun thi phi p ng yu cu cua php th ny.

nh lng
Phng php sc k lng (Ph lc 5.3).
Pha ng: Ha tan 2,0 g tris(hydroxymethyl)aminoethan (TT) trong 800 ml nc. Thm 20 ml dung
dch acid sulfuric 0,5 M (TT) vo dung dich thu c v pha long thnh 2000 ml bng acetonitril (TT).
ngui, lc qua mng lc 0,2 m. iu chnh nu cn.
Thuc th 2,4-dinitroflourobenzen: Pha dung dich 2,4-dinitroflourobenzen (TT) c nng 10 mg/ml
trong ethanol 96 % (TT). Dung dich c dng trong vng 5 ngy sau khi pha, bo qun trong tu lanh.
Thuc th tris(hydroxymethyl)aminomethan: Pha dung dich chun gc cha tris(hydroxymethyl)
aminomethan (TT) nng 15 mg/ml trong nc. Dung dich ny dng c trong vng 1 thng, bo
qun trong tu lanh. Ly 40 ml dung dich chun gc vo binh inh mc 200 ml, thm dimethyl sulfoxid
(TT) v trn u, thm dimethyl sulfoxid (TT) n vanh. Thuc th ny c dng trong vng 4 h. (Nu
nhung chim trong nc nhit di 10 C thi c th dng thuc th ny trong vng 8 h).
Dung dch th: Cn chinh xc khong 55 mg ch phm vo binh inh mc 50 ml, thm 1 ml dung dch
acid sulfuric 1 M (TT) v thm nc ha tan ch phm, sau thm nc n vach. Pha long 10,0
ml dung dich thu c thnh 50 ml bng nc.
Dung dch chun: Cn chinh xc khong 55 mg tobramycin chun vo binh inh mc 50 ml, thm 1 ml
dung dch acid sulfuric 0,5 M (TT) v thm nc ha tan ch phm, sau thm nc n vach.
Pha long 10,0 ml dung dich thu c thnh 50 ml bng nc.

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Tao dn xut: [Chu : lm nng cc dung dich cng nhit , cng thi gian. Cc binh c t vo
v ly ra khi b cch thuy (c duy tri nhit 60 C) ng thi]. Ln lt thm vo 3 binh inh
mc khc nhau 4,0 ml dung dich chun; 4,0 ml dung dich th v 4,0 ml nc. Thm vo mi binh 10
ml thuc th 2,4-dinitroflourobenzen v 10 ml thuc th tris(hydroxymethyl)aminomethan, lc u v
y np binh. cc binh vo b cch thuy c duy tri 60 C 2 C trong 50 min 5 min. Ly binh
ra, yn 10 min. Thm acetonitril (TT) n gn vach (cch vach khong 2 ml), ngui v nhit
phng v thm acetonitril (TT) n vach, lc u. Cc dung dich thu c sau khi tao dn xut ln lt
l cc dung dich dn xut chun, dung dich dn xut th v dung dich mu trng.
Dung dch phn gii: Chun bi dung dich mi pha p-naphtholbenzen (TT) c nng 0,24 mg/ml trong
acetonitril (TT). Pha long 2 ml dung dich thu c thnh 10 ml bng dung dich dn xut chun.
iu kin sc k:
Ct kich thc 30 cm 3,9 mm c nhi pha tnh C.
Detector quang ph hp th t ngoai t bc sng 365 nm.
Tc dng: 1,2 ml/min.
Th tich tim: 20 l.
Cch tin hnh:
Tin hnh sc k vi dung dich mu trng xc inh pic dung mi v pic thuc th.
Tin hnh sc k vi dung dich phn gii, thi gian lu tng i cua pic p-naphatholbenzein so vi
pic tobramycin khong 0,6. phn gii gia pic p-naphatholbenzein v pic tobramycin it nht l 4,0.
Tin hnh sc k vi dung dich dn xut chun, lch chun tng i cua din tich pic t 6 ln tim
lp lai dung dich chun khng c ln hn 2,0 %.
Tin hnh sc k vi dung dich dn xut th v dung dich dn xut chun.
Tinh hm lng tobramycin C18H37N5O9 trong ch phm da vo din tich pic p ng thu c t
dung dich dn xut chun, dung dich dn xut th v hm lng C18H37N5O9 cua tobramycin chun.

Bo qun
Nu ch phm v khun, phi bo qun trong bao bi kin, v khun.

Loi thuc
Khng sinh nhm aminoglycosid.

Ch phm
Thuc tim, thuc nh mt.

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