EUROPEAN PHARMACOPOEIA 5.8
Thioridazine
- Detectio n: spectrophotometer at 240 nm.
- C. R = CO-C2H5 : testosterone propionate,
Injectio n: 20 µl of the test solution and reference
D. R = CO-CH(CH3)2 : 3-oxoandrost-4-en-17β-yl
solutions (a) and (b).
2-methylpropanoate (testosterone isobutyrate),
Run tim e: twice the retention time of testosterone isocaproate.
Identification of impuritie s: use the chromatogram supplied with testosterone isocaproate for system suitability CRS
and the chromatogram obtained with reference solution (a) to identify the peaks due to impurities A, B, C, D, E, F and G.
E. R = CO-[CH2]4-CH3 : 3-oxoandrost-4-en-17β-yl hexanoate
(testosterone caproate),
F. R = CO-[CH2]5-CH3 : testosterone enantate,
Relative retention with reference to testosterone isocaproate (retention time = about 14 min): impurity A = about 0.2; impurity B = about 0.4; impurity C = about 0.5; impurity D = about 0.7; impurity G = about 0.8; impurity E = about 1.1; impurity F = about 1.4.
System suitabilit y: reference solution (a):
G. 3-oxoandrost-4-en-17α-yl 4-methylpentanoate
— peak-to-valley rati o: minimum 2.5, where Hp = height
above the baseline of the peak due to impurity E and Hv = height above the baseline of the lowest point of the curve separating this peak from the peak due to testosterone isocaproate.
(epitestosterone isocaproate).
07/2007:2005
THIORIDAZINE
Limit s: — impurities A, B, C, D, E, F, G: for each impurity, not more
than the area of the principal peak in the chromatogram obtained with reference solution (b) (0.5 per cent);
— unspecified impuritie s: for each impurity, not more
than 0.2 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.10 per cent);
Thioridazinum
— tota l: not more than twice the area of the principal peak in the chromatogram obtained with reference solution (b) (1.0 per cent);
— disregard limi t: 0.1 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.05 per cent).
C21H26N2S2
Mr 370.6
DEFINITION 10-[2-[(2RS)-1-Methylpiperidin-2-yl]ethyl]-2- (methylsulphanyl)-10H-phenothiazine
Free acid. Dissolve 0.44 g in 10 ml of ethanol (96 per
cent) R, previously neutralised to bromothymol blue solution R3, and titrate immediately with 0.01 M sodium hydroxide, using 0.1 ml of bromothymol blue solution R3 as
indicator. Not more than 0.6 ml of 0.01 M sodium hydroxide is required to change the colour of the indicator to blue.
Conten t: 99.0 per cent to 101.0 per cent (dried substance). CHARACTERS Appearanc e: white or almost white powder.
Loss on drying (2.2.32): maximum 0.5 per cent, determined
on 1.000 g over diphosphorus pentoxide R at a pressure
not exceeding 0.7 kPa.
Solubilit y: practically insoluble in water, very soluble in methylene chloride, freely soluble in methanol, soluble in ethanol (96 per cent).
ASSAY
IDENTIFICATION Infrared absorption spectrophotometry (2.2.24).
Liquid chromatography (2.2.29) as described in the test for related substances with the following modification.
Injectio n: 20 µl of the test solution and reference solution (c). Compariso n: thioridazine CRS.
Calculate the percentage content of C25H38O3 from the
declared content of testosterone isocaproate CRS.
TESTS Solution S. Dissolve 1.25 g in methanol R and dilute to 25 ml with the same solvent.
IMPURITIES
Specified impuritie s: A, B, C, D, E, F, G.
Appearance of solution. Solution S is clear (2.2.1) and not
more intensely coloured than intensity 6 of the range of reference solutions of the most appropriate colour (2.2.2,
Method II).
Related substances. Liquid chromatography (2.2.29). Carry
out the test as quickly as possible and protected from light.
Test solution. Dissolve 20 mg of the substance to be examined in methanol R and dilute to 100 ml with the same solvent. Reference solution (a). Dilute 5.0 ml of the test solution to 100.0 ml with methanol R. Dilute 2.0 ml of this solution to
100.0 ml with methanol R.
A. R = H: testosterone, B. R = CO-CH3 : 3-oxoandrost-4-en-17β-yl acetate
(testosterone acetate),
General Notices (1) apply to all monographs and other texts
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Tranexamic acid
EUROPEAN PHARMACOPOEIA 5.8
Reference solution (b). Dissolve the contents of a vial
of thioridazine for system suitability CRS (containing
impurities A, B, C, D and E) in 1.0 ml of methanol R.
ASSAY Dissolve 0.300 g in 60 ml of anhydrous acetic acid R. Titrate with 0.1 M perchloric acid, determining the end-point potentiometrically (2.2.20).
Colum n:
1 ml of 0.1 M perchloric acid is equivalent to 37.06 mg
— siz e: l = 0.25 m, Ø = 4.0 mm;
of C21H26N2S2.
— stationary phas e: end-capped octadecylsilyl silica gel
- for chromatography R resistant to bases up to pH 11.
- STORAGE
Protected from light.
Mobile phas e: — mobile phase A: triethylamine R1, acetonitrile R,
IMPURITIES
Specified impuritie s: A, B, C, D, E. water R (2:400:600 V/V/V);
— mobile phase B: triethylamine R1, acetonitrile R
Other detectable impurities (the following substances
would, if present at a sufficient level, be detected by one or other of the tests in the monograph. They are limited by the general acceptance criterion for other/unspecified impurities and/or by the general monograph Substances for pharmaceutical use (2034). It is therefore not necessary to identify these impurities for demonstration of compliance.
See also 5.10. Control of impurities in substances for pharmaceutical use): F.
(2:1000 V/V);
Time (min)
0 - 5
Mobile phase A (per cent V/V)
100
Mobile phase B (per cent V/V)
0
5 - 35 35 - 40 40 - 41
41
100 → 5
5
0 → 95
95
5 → 100
100
95 → 0
0
Flow rat e: 1.0 ml/min.
Detectio n: spectrophotometer at 275 nm.
Injectio n: 25 µl. Identification of impuritie s: use the chromatogram supplied with thioridazine for system suitability CRS and
the chromatogram obtained with reference solution (b) to identify the peaks due to impurities A, B, C, D and E.
A. R = CH3, X = X′ = SO2 : 10-[2-[(2RS)-1-methylpiperidin-
2-yl]ethyl]-2-(methylsulphonyl)-10H-phenothiazine 5,5-dioxide,
Relative retention with reference to thioridazine (retention time = about 30 min): impurity D = about 0.1; impurity A = about 0.3; impurity C = about 0.4; impurity B = about 0.5; impurity E = about 0.6.
B. R = CH3, X = SO, X′ = S: 10-[2-[(2RS)-1-methylpiperidin-
2-yl]ethyl]-2-(methylsulphinyl)-10H-phenothiazine (mesoridazine),
C. R = CH3, X = S, X′ = SO: 10-[2-[(2RS)-1-methylpiperidin-2-
System suitabilit y: reference solution (b):
yl]ethyl]-2-(methylsulphanyl)-10H-phenothiazine 5-oxide,
— resolutio n: minimum 3.5 between the peaks due to
D. R = CH3, X = X′ = SO: 10-[2-[(2RS)-1-methylpiperidin-2- impurities C and B.
yl]ethyl]-2-(methylsulphinyl)-10H-phenothiazine 5-oxide,
Limit s:
E. R = CH3, X = SO2, X′ = S: 10-[2-[(2RS)-1-methylpiperidin-
2-yl]ethyl]-2-(methylsulphonyl)-10H-phenothiazine (sulforidazine),
— correction factor s: for the calculation of content, multiply the peak areas of the following impurities by the corresponding correction factor: impurity A = 1.9; impurity B = 2.4; impurity C = 0.5; impurity D = 1.5;
F. R = H, X = X′ = S: 2-(methylsulphanyl)-10-[2-[(2RS)-
piperidin-2-yl]ethyl]-10H-phenothiazine (northioridazine).
— impurities A, B, C, D, E: for each impurity, not more
than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.1 per cent);
07/2007:0875
TRANEXAMIC ACID
— unspecified impuritie s: for each impurity, not more
than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.10 per cent);
— tota l: not more than 5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.5 per cent);
Acidum tranexamicum
— disregard limi t: 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.05 per cent).
Heavy metals (2.4.8): maximum 20 ppm.
1.0 g complies with test C. Prepare the reference solution
using 2 ml of lead standard solution (10 ppm Pb) R.
C8H15NO2
Mr 157.2
Loss on drying (2.2.32): maximum 0.5 per cent, determined on 1.000 g in vacuo at 50 °C for 4 h.
DEFINITION trans-4-(Aminomethyl)cyclohexanecarboxylic acid. Conten t: 99.0 per cent to 101.0 per cent (dried substance).
Sulphated ash (2.4.14): maximum 0.1 per cent, determined on 1.0 g.
5382
See the information section on general monographs (cover pages)
