TIMOLOL MALEAT

Timololi maleas

 

 

 

 

 

 

 

 

 


C13H24N4O3S.C4H4O4 P.t.l: 432,5

Timolol maleat la (2S)-1-[(1,1-dimethylethyl)amino]-3-[[4-(morpholin-4-yl)-1,2,5-thiadiazol-3-yl]oxy]propan-2-ol (Z)-butenedioat, phai cha t 98,5 en 101,0% C13H24N4O3S.C4H4O4, tnh tren che pham a lam kho.

Tnh chat

Bot ket tinh trang hay gan nh trang hoac tinh the khong mau. Tan trong nc va ethanol 96%, thc te khong tan trong ether. Nong chay 199 oC kem theo s phan huy.

nh tnh

Co the chon mot trong hai nhom nh tnh sau:

Nhom I: A, B

Nhom II: A, C, D

A. Hoa tan 1,000 g che pham trong dung dch acid hydrocloric 1 M va pha loang thanh 10 ml vi cung dung moi. Goc quay cc rieng (Phu luc 6.4) t 5,7 en 6,2 o.

B. Pho hong ngoai (Phu luc 4.2) cua che pham phai phu hp vi pho hong ngoai cua timolol maleat chuan (C).

C. Kiem tra sac ky o thu c muc th Tap chat lien quan sau khi tiep xuc vi hi iod. Vet chnh trong sac ky o cua dung dch th (2) phai giong ve mau sac, v tr va kch thc cua vet chnh trong sac ky o cua dung dch oi chieu (1).

D. Nghien 0,1 g che pham vi hon hp cha 1 ml dung dch natri hydroxyd loang (TT) va 3 ml nc. Lac hon hp tren 3 lan vi ether, moi lan 5 ml. Lay 0,1 ml lp nc, them vao dung dch cha 10 mg resorcinol (TT) trong 3 ml acid sulfuric (TT). un tren cach thuy 15 phut. Khong xuat hien mau o tm. Trung hoa phan con lai cua lp nc vi acid sulfuric loang (TT) va them 1 ml nc brom (TT). un cach thuy 15 phut, sau o un en soi va e nguoi. Lay 0,2 ml dung dch nay, them vao dung dch cha 10 mg resorcinol (TT) trong 3 ml acid sulfuric (TT). un cach thuy 15 phut. Xuat hien mau o tm. Them 0,2 ml dung dch kali bromid 10% (TT), un cach thuy 5 phut, dung dch chuyen sang mau xanh tm.

o trong va mau sac cua dung dch

Dung dch S: Hoa tan 0,5 g che pham trong nc khong co carbon dioxyd (TT) va pha loang thanh 25 ml vi cung dung moi.

Dung dch S phai trong (Phu luc 9.2) va khong c am mau hn dung dch N8 (Phu luc 9.3 phng phap 2).

pH

pH cua dung dch S phai t 3,8 4,3 (Phu luc 6.2).

Tap chat oi quang

Khong c qua 1%.

Tien hanh bang phng phap sac ky long (Phu luc 5.3) trong ieu kien tranh anh sang.

Pha ong: Diethylamin - 2-propanol - hexan (2 : 40 : 960).

Dung dch th: Hoa tan 30,0 mg che pham trong hon hp methylen clorid - 2-propanol (1 : 3) va pha loang thanh 10 ml vi cung dung moi.

Dung dch oi chieu (1): Hoa tan 30 mg timolol maleat chuan (C) trong hon hp methylen clorid - 2-propanol (1 : 3) va pha loang thanh 10 ml vi cung dung moi.

Dung dch oi chieu (2): Hoa tan 15,0 mg (R)-timolol maleat chuan (C) trong hon hp methylen clorid - 2-propanol (1 : 3) va pha loang thanh 10 ml vi cung dung moi. Pha loang 1 ml dung dch tren thanh 50 ml vi cung dung moi.

Dung dch phan giai: Pha loang 1 ml dung dch oi chieu (1) thanh 100 ml bang hon hp methylen clorid - 2-propanol (1 : 3). Tron eu 1 ml dung dch nay vi 1 ml dung dch oi chieu (2).

ieu kien sac ky:

Cot thep khong g (0,25 m x 4,6 mm) c nhoi silica gel OD dung e tach oi quang R (5 mm).

Toc o dong: 1 ml/phut.

Detector quang pho hap thu t ngoai 297 nm.

The tch tiem: 5 ml

ieu kien nay pic ng vi ong phan (R) se xuat hien trc.

Cach tien hanh: Tiem dung dch oi chieu (2). ieu chnh o nhay cua he thong sao cho chieu cao cua pic chnh trong sac ky o t nhat bang 50% cua thang o. Tiem tng dung dch tren. Phep th ch co gia tr neu o phan giai gia cac pic ng vi ong phan (R) va (S) trong sac ky o dung dch phan giai t nhat la 4,0; thi gian lu cac pic chnh (ng vi ong phan S) c xac nh bang thi gian lu cua pic chnh trong sac ky o dung dch th va dung dch oi chieu (1).

Dien tch cua bat ky pic nao ng vi ong phan R trong sac ky o dung dch th khong c ln hn dien tch pic chnh cua dung dch oi chieu (2) (1%).

Tap chat lien quan

Khong c qua 0,4%.

Tien hanh bang phng phap sac ky lp mong. (Phu luc 5.4)

Ban mong: Silica gel GF254 (TT).

Dung moi khai trien: Amoniac methanol methylen clorid (1 : 20 : 80)

Dung dch th (1): Hoa tan 0,50 g che pham trong methanol (TT) va pha loang thanh 10 ml vi cung dung moi.

Dung dch th (2): Pha loang 1 ml dung dch th (1) thanh 50 ml bang methanol (TT) .

Dung dch oi chieu (1): Hoa tan 10 mg timolol maleat chuan (C) trong methanol (TT) va pha loang thanh 10 ml vi cung dung moi.

Dung dch oi chieu (2): Pha loang 10 ml dung dch th (2) thanh 50 ml bang methanol (TT).

Cham rieng biet len ban mong 10 ml moi dung dch. Trien khai sac ky en khi dung moi i c 15 cm. Lay ban mong ra, e kho ngoai khong kh va quan sat di anh sang en t ngoai bc song 254 nm. Bat c vet nao (ngoai vet chnh) trong sac ky o dung dch th (1) khong c am mau hn vet trong sac ky o dung dch oi chieu (2) (0,4%). Khong ke en vet vach xuat phat. Cho ban mong tiep xuc vi hi iod trong 2 gi. Bat c vet nao (ngoai vet chnh) trong sac ky o dung dch th (1) khong c am mau hn vet trong sac ky o dung dch oi chieu (2) (0,4%). Khong ke en vet vach xuat phat.

Mat khoi lng do lam kho

Khong c qua 0,5%(Phu luc 9.6).

(1,000 g, 100 105 oC).

Tro sulfat

Khong c qua 0,1 % ( Phu luc 9.9 phng phap 2).

Dung 1,0 g che pham.

nh lng

Hoa tan 0,35 g che pham trong 60 ml acid acetic khan (TT). Chuan o bang dung dch acid percloric 0,1 M (C), iem ket thuc c xac nh bang phng phap chuan o o ien the (Phu luc 10.2).

1 ml dung dch acid percloric 0,1 M (C) tng ng vi 43,25 mg C13H24N4O3S.C4H4O4.

Bao quan

e trong lo kn, tranh anh sang.

Loai thuoc

Khang beta adrenoreceptor.

Che pham

Thuoc nho mat, vien nen.