Zidovudin

Zidovudinum

C10H13N5O4 P.t.l: 267,2

Zidovudin la 1-(3-azido-2,3-dideoxy-b-D-erythro-pentofuranosyl)-5-methylpyrimidin-2,4-(1H,3H)-dion, phai cha t 97,0 en 102 % C10H13N5O4 tnh theo che pham a lam kho.

Tnh chat

Bot trang hoac anh nau. Hi tan trong nc, tan trong ethanol. iem chay khoang 124 oC. Dang vo nh hnh.

nh tnh

Pho hong ngoai (Phu luc 4.2) cua che pham phai phu hp vi pho hong ngoai cua zidovudin chuan (C). Neu pho thu c t dang ran co s khac biet, tien hanh hoa tan che pham va chat chuan rieng re trong mot lng toi thieu nc sau o bay hi en kho trong bnh hut am di ap suat giam va co mat cua diphosphor pentoxyd (TT). Ghi va so sanh pho mi cua cac can thu c.

Mau sac cua dung dch

Hoa tan 0,5 g che pham trong 50 ml nc, un nong neu can thiet. Mau cua dung dch thu c khong c am hn mau mau VN5 (Phu luc 9.3; Phng phap 2).

Goc quay cc rieng

T + 60,5o en + 63,0o, tnh theo che pham a lam kho (Phu luc 6.4).

Hoa tan 0,50 g che pham trong ethanol (TT) va pha loang thanh 50,0 ml vi cung dung moi. Dung dung dch thu c o 25 oC.

Tap chat lien quan

A. Kiem tra bang phng phap sac ky lp mong (Phu luc 5.4)

Ban mong: Silica gel GF 254 (TT).

Dung moi trien khai: Methanol - methylen clorid (10 : 90).

Dung dch th : Hoa tan 0,2 g che pham trong methanol (TT) va pha loang thanh 10 ml vi cung dung moi.

Dung dch oi chieu (1): Hoa tan 20 mg moi chat sau ay: thymin (TT), tap chat oi chieu A cua zidovudin, triphenylmethanol (TT) trong methanol (TT), them 1,0 ml dung dch th va pha loang thanh 100 ml bang methanol (TT).

Dung dch oi chieu (2): Pha loang 5,0 ml dung dch oi chieu (1) thanh 10 ml vi methanol (TT).

Cach tien hanh:

Cham rieng re len ban mong 10 l moi dung dch tren. Trien khai sac ky en khi dung moi di chuyen c 12 cm. Lam kho ban mong ngoai khong kh, quan sat di anh sang UV 254 nm. Tren sac ky o cua dung dch th: vet phu tng ng vi tap chat A cua zidovudin khong c am mau hn vet tng ng tren sac ky o thu c t dung dch oi chieu (2) (0,5%), va bat c vet phu nao khac ngoai vet chnh, va cac vet tng ng vi tap chat A cua zidovudin, thymin (chat nay kiem gii han bang sac ky long) eu khong c am mau hn vet tng ng zidovudin tren sac ky o thu c t dung dch oi chieu (2) (0,5%). Phun ban mong vi dung dch vanillin 1% (kl/tt) (TT) pha trong acid sulfuric (TT). Tren sac ky o cua dung dch th, vet tng ng vi triphenylmethanol khong c am mau hn vet tng ng thu c dung dch oi chieu (2) (0,5%). Th nghiem ch co gia tr khi sac ky o cua dung dch oi chieu (1) co 4 vet tach biet ro rang tng ng vi thymin, tap chat A cua zidovudin, zidovudin, va triphenylmethanol theo th t Rf tang dan.

B. Kiem tra bang phng phap sac ky long

Tien hanh theo mo ta trong phan nh lng.

Tiem rieng re 10 l moi dung dch: Dung dch th (1), dung dch oi chieu (2), dung dch oi chieu (4) va dung dch oi chieu (5). Thc hien sac ky vi thi gian gap 1,5 lan thi gian lu cua pic chnh trong sac ky o cua dung dch th (1). Khi sac ky o ghi c trong ieu kien nh mo ta, cac chat xuat hien theo th t thymin, zidovudin, tap chat B cua zidovudin. Trong sac ky o cua dung dch th (1): dien tch cua bat c pic nao tng ng vi thymin khong c ln hn dien tch pic thu c t dung dch oi chieu (2) (2%); dien tch cua pic tng ng vi tap chat B cua zidovudin khong c ln hn dien tch pic tng ng tren sac ky o cua dung dch oi chieu (4) (1%); dien tch cua bat c pic phu nao khac tr pic chnh, khong c ln hn dien tch pic thu c t dung dch oi chieu (5) (0,5%). Tong dien tch cua tat ca cac pic khac vi vet chnh tren sac ky o thu c t dung dch th (1) khong c ln hn 6 lan so vi dien tch pic thu c t dung dch oi chieu (5) (3,0%). Bo qua cac pic co dien tch nho hn 10% so vi dien tch pic tren sac ky o thu c t dung dch oi chieu (5).

Kim loai nang

Khong c qua 20 phan trieu, dung 1,0 g che pham tien hanh th nghiem. (Phu luc 9.4.8; Phng phap 4).

Dung 2 ml dung dch ch mau 10 phan trieu (TT) e chuan b mau oi chieu.

Mat khoi lng do lam kho

Khong c qua 1,0 % (Phu luc 9.6).

(1,000 g; 100 105 oC).

Tro sulfat

Khong c qua 0,25 %, (Phu luc 9.9, phng phap 2).

Dung 1,0 g che pham

nh lng

Tien hanh theo phng phap sac ky long (Phu luc 5.3)

Pha ong: Methanol nc (20 : 80)

Dung dch th (1): Hoa tan 50,0 mg che pham trong pha ong va pha loang thanh 50,0 ml vi pha ong.

Dung dch th (2): Pha loang 10,0 ml dung dch th (1) thanh 50,0 ml bang pha ong.

Dung dch oi chieu (1): Hoa tan 10,0 mg zidovudin chuan (C) trong pha ong va pha loang thanh 50,0 ml vi cung dung moi.

Dung dch oi chieu (2): Hoa tan 10,0 mg thymin (TT) trong methanol (TT) va pha loang thanh 50,0 ml vi cung dung moi. Pha loang 5,0 ml dung dch nay thanh 50,0 ml bang pha ong.

Dung dch oi chieu (3): Hoa tan 5,0 mg tap chat chuan B cua zidovudin (C) trong 25,0 ml dung dch oi chieu (1) va pha loang thanh 50,0 ml vi pha ong.

Dung dch oi chieu (4): Pha loang 5,0 ml dung dch oi chieu (3) thanh 50,0 ml bang pha ong.

Dung dch oi chieu (5): Pha loang 0,25 ml dung dch th (1) thanh 50,0 ml bang pha ong.

ieu kien sac ky:

Cot thep khong r (0,25 m x 4,6 mm) c nhoi pha tnh C (5 m).

Toc o dong: 1,2 ml/phut.

The tch tiem: 10 l.

Detector quang pho hap thu t ngoai at bc song 265 nm.

Cach tien hanh:

On nh cot vi pha ong toc o dong 1,2 ml / phut trong 45 phut.

Tiem 10 l dung dch oi chieu (3). ieu chnh o nhay cua detector sao cho chieu cao cua pic chnh tren sac ky o thu c khong nho hn 70% cua thang o. Phep th ch co gia tr kh o phan giai gia cac pic cua zidovudin va tap chat B t nhat bang 1,0. Tiem dung dch th (2) va dung dch oi chieu (1). ieu chnh o nhay cua detector sao cho chieu cao cua pic tren sac ky o thu c khong nho hn 50% cua thang o.

Tnh ham lng cua C10H13N5O4 t dien tch cua cac pic va t ham lng cua zidovudin trong dung dch oi chieu (1).

Ghi chu:

Tap chat A: 1-[(2R,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl)-5-methyl-pyrimidin-2,4(1H,3H)dion

Tap chat B: 1-(3-cloro-2,3-dideoxy-b-D-erythro-pentofuranosyl)-5-methyl-pyrimidin-2,4-(1H,3H)dion.

Bao quan

Tranh anh sang.

Loai thuoc

Khang virus.