DOXOFYLLINE
IP 2010
Doxofylline
Mol. Wt. 266.3
Doxofylline is 7-(1,3-dioxolan-2-ylmethyl)-3,7-dihydro-l,3-
dimethyl-lH-purine-2,6-dione.
Doxofylline contains not less than 98.0 per cent and not more
than 102.0 per cent of C ll H 14N40 4, calculated on the dried
basiS:--
Category. Bronchodilator.
Description. A white to off white crystalline powder.
Identification
A. Determine by infrared absorption spectrophotometry (2.4.6).
Compare the spectrum obtained with doxofylline RS or with
the reference spectrum of doxofylline.
B. When examined in the range of 200 nm to 400 om (2.4.7), a
-0,001 per centw/v solution in water shows·-an-absorption
maximum at about 274 om.
Tests
Related substances. Determine by liquid chromatography
(2.4.14).
Test solution. Dissolve 0.1 g of the substance under
examination in 100,0 ml ofthe mobile phase.
Reference solution (a). A solution containing 0.05 per cent wi
veach of doxofylline RS and theophylline RS in the mobile Inject reference solution (b). The test is not valid unless the
phase·.- "" """.. --.- " llieoreticarplatesis:iiot1essllian2000~llieTiill.ii1g factofiS-noC
Reference solution (b). Dilute 1.0 ml of reference solution (a)
to 100.0 ml with the mobile phase.
Chromatographic system
a stainless steel column 25 cm x 4.6 mID, packed with
octadecylsilane bonded to porous silica (5 1JIIl) (such as
Cosmosil CI8),
"mooile-pnase:-amix:t:Ufeof-80-volume~mfwateYaha·20
volumes of acetonitrile,
- flow rate. 0.8 ml per minute,
- spectrophotometer set at 274 om,
- injection volume. 20 f.ll.
Inject reference solution (b). The test is not valid unless the
resolution between the peaks due to theophylline and
1254
doxofylline is not less than 5.0 and the relative standard
deviation for replicate injections is not more than 5.0 per cent.
Inject reference solution (b) and the test solution. In the
chromatogram obtained with the test solution, the area of the
peak due to theophylline is not more than the area of the
corresponding peak in the chromatogram obtained with
reference solution (b) (0.5 per cent) and the area of any other
secondary peak is not more than the area of the peak in the
chromatogram obtained reference solution (b) (0.5 per cent).
The sum of areas of all the secondary peaks is not more than
twice the area of the peak in the chromatogram obtained
reference solution (b) (1.0 per cent).
Heavy Metals (2.3.13). 1.0 g complies with the limit test for
heavy metals, Method B (20 ppm).
Sulphated ash (2.3.18). Not more than 0.2 per cent.
Loss on drying (2.4.19). Not more than 0.5 per cent, determined
on 1.0 g by drying in oven at 105° for 3 hours.
Assay. Determine by liquid chromatography (2.4.14).
Test solution. Dissolve about 40 mg of substance under
examination in 100.0 ml of the mobile phase. Dilute 5.0 ml of
this solution to 50.0 ml with the mobile phase.
Reference solution. A 0.004 per cent wlv solution of
doxofylline RS in the mobile phase.
Chromatographic system
_" "._ a. stainless.steel CQlumn25cIl1x:4.6rnp1,R!l<::kec:l" with
octadecylsilane bonded to porous silica (51JIIl) (such as
Cosmosil CI8),
mobile phase: a mixture of80 volumes ofa buffer solution
prepared by dissolving 6.8 g of potassium dihydrogen
orthophosphate in 1000 ml of water, and 20 volumes of
acetonitrile,
- flow rate. 1 ml per minute,
- spectrophotometer set at 274 om,
- injection volume. 10 f.ll.
more than 2.0 and therelative standard deviation for replicate
injections is not more than 2.0.
Inject reference solution (b) and the test solution.
Calculate the content of CllHl~404'
Storage. Store protected from light and moisture, at a
temperature not exceeding 30°.
Doxofylline Tablets
Doxofylline Tablets contain not less than 95.0 per cent and
not more than 105.0 per cent of the stated amount of
doxofylline, CllHl~404'
IP 2010
Usual strength. 400 mg.
Identification
A. Extract a quantity of the powdered tablets containing about
0.1 g of Doxofylline with 40 ml of chloroform, f1lter and
evaporate the f1ltrate to dryness. On the residue, determine by
infrared absorption spectrophotometry (2.4.6). Compare the
spectrum with that obtained from doxofylline RS or with the
reference spectrum of doxofylline.
B. In the Assay, the principal peak in the chromatogram
obtained with the test solution corresponds to the peak in the
chromatogram obtained with the reference solution.
Tests
Dissolution (2.5.2).
Apparatus No.1,
Medium. 900 ml of 0.01 M hydrochloric acid,
Speed and time. 50 rpm and 45 minutes.
Withdraw a suitable volume of the medium and f1lter through
a membrane f1lter. Measure the absorbance of the f1ltered
solution, suitably diluted if necessary with the medium, at the
maximum at about 275 nm (2.4.7). Calculate the content
of CllHl~404 in the medium from the absorbance obtained
from a solution of known concentration of doxofylline RS in
the same medium.
D. Not less than 75 per cent of the stated amount of
CllHl~404'
Related suhstances. Determine by liquid chromatography
(2.4.14).
Test solution. Disperse a quantity of powdered tablets
containing about 25 mg ofDoxofylline in 25.0 ml in the mobile
phase and fIlter.
Reference solution (a). A 0.1 per cent w/v solution of
doxofylline RS in the mobile phase.
Reference solution (b). Dilute 1.0 ml of reference solution (a)
to 100.0 ml with the mobile phase.
.Use chromatographic system as described under Assay.
Inject reference solution (a). The test is not valid unless the
tailing factor is not more than 2.0, theoretical plates is not less
than 1500 and the relative standard deviation for replicate
injections is not more than 2.0 per cent.
Inject reference solution (b) and the test solution. In the
chromatogram obtained with the test solution, the area of any
secondary peak is not more than 0.2 times the area of the peak
obtained with reference solution (b) (0.2 per cent) and the sum
of areas of all the secondary peaks is not more than the area of
the peak in the chromatogram obtained with reference solution
(b) (1.0 per cent).
1255
DOXORUBICIN HYDROCHLORIDE
Other tests. Comply with the tests stated under Tablets.
Assay. Determine by liquid chromatography (2.4.14).
Test solution (a). Weigh and powder 20 tablets. Disperse a
quantity of powder containing about 50 mg of Doxofylline in
70 ml of methanol, sonicate for 15 minutes and dilute to 100 ml
with methanol, fIlter.
Test solution (b). Dilute 2.0 ml of test solution (a) to 50.0 ml
with the mobile phase.
Reference solution (a). A 0.05 per cent w/v solution of
doxofylline RS in methanol.
Reference solution (b). Dilute 2.0 ml of reference solution(a)
to 50.0 ml with the mobile phase.
Chromatographic system
a stainless steel column 25 cm x 4.6 rom, packed with
octadecylsilane bonded to porous silica (5 fJIll),
- mobile phase: a mixture of 30 volumes of water and 70
volumes of methanol,
- flow rate. 1 ml per minute,
spectrophotometer set at 274 urn,
injection volume. 20 J1l.
Inject reference solution (b). The test is not valid unless the
tailing factor is not more than 2.0, theoretical plates is not less
than 1500 and the relative standard deviation for replicate
injections is not more than 2.0 per cent.
Inject reference solution (b) and test solution (b).
Calculate the content of CllH14N404 in the tablets.
Storage. Store protected from light and moisture.
Doxorubicin Hydrochloride
o OH o
OH
,HCI
HsCO
C27H29NOll,HCl Mol. Wt. 580.0
Doxorubicin Hydrochloride is (8S,10S)-1O-[(3-arnino~2,3, 6-
trideoxy-a. -L-Iyxo-hexopyranosyl)oxy]-6,8,II-trihydroxy- 8-
hydroxyacetyl-l-methoxy-7,8,9,1O-tetrahydronaphthacene-
5,12-dione hydrochloride, a substance produced by the growth
of certain strains of Streptomyces coeruleorubidus or S.
peucetius or obtained by any other means.