Thioctic acid EUROPEAN PHARMACOPOEIA 10.

E. N-[(7S,12aRa)-3-(β-D-glucopyranosyloxy)-1,2-
dimethoxy-10-(methylsulfanyl)-9-oxo-5,6,7,9-
tetrahydrobenzo[a]heptalen-7-yl]formamide
(N-deacetyl-N-formylthiocolchicoside),

K. N-[(7S,12aRa)-3-(β-D-glucopyranosyloxy)-2-hydroxy-
1-methoxy-10-(methylsulfanyl)-9-oxo-5,6,7,9-
tetrahydrobenzo[a]heptalen-7-yl]acetamide or
N-[(7S,12aRa)-3-(β-D-glucopyranosyloxy)-1-hydroxy-
2-methoxy-10-(methylsulfanyl)-9-oxo-5,6,7,9-
tetrahydrobenzo[a]heptalen-7-yl]acetamide,

G. (7S,12aRa)-7-amino-3-(β-D-glucopyranosyloxy)-1,2-
dimethoxy-10-(methylsulfanyl)-6,7-dihydrobenzo[a]-
heptalen-9(5H)-one (N-deacetylthiocolchicoside),

L. N-[(7S,12aSa)-3-(β-D-glucopyranosyloxy)-1,2-
dimethoxy-10-(methylsulfanyl)-9-oxo-5,6,7,9-
tetrahydrobenzo[a]heptalen-7-yl]acetamide
(12aSa-thiocolchicoside).

01/2008:1648

THIOCTIC ACID
H. N-[(7S,12aRa)-3-(β-D-glucopyranosyloxy)-1,2-dimethoxy-
9-oxo-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]acetamide
(10-demethoxycolchicoside), Acidum thiocticum

C8H14O2S2 Mr 206.3
[1077-28-7]
DEFINITION
5-[(3RS)-1,2-Dithiolan-3-yl]pentanoic acid.
Content : 97.0 per cent to 102.0 per cent (dried substance).
CHARACTERS
Appearance : yellow, crystalline powder.
Solubility : very slightly soluble in water, very soluble in
dimethylformamide, freely soluble in methanol.
mp : about 61 °C.
J. N-[(7S,12aRa)-3-(β-D-glucopyranosyloxy)-1,2- IDENTIFICATION
dimethoxy-10-(methylsulfinyl)-9-oxo-5,6,7,9-
tetrahydrobenzo[a]heptalen-7-yl]acetamide Infrared absorption spectrophotometry (2.2.24).
(thiocolchicoside S-oxide), Comparison : thioctic acid CRS.

4020 See the information section on general monographs (cover pages)

EUROPEAN PHARMACOPOEIA 10.0
TESTS
Appearance of solution. The solution is clear (2.2.1).
Dissolve 0.50 g in a 20 g/L solution of sodium hydroxide R and
dilute to 10 mL with the same solution.
Impurity B. Thin-layer chromatography (2.2.27).
Test solution. Dissolve 0.20 g of the substance to be examined
in dimethylformamide R and dilute to 10 mL with the same
solvent.
Reference solution. Dissolve 20 mg of thioctic acid containing
impurity B CRS in dimethylformamide R and dilute to 1.0 mL
with the same solvent (1.0 per cent impurity B solution).
Plate : TLC silica gel plate R.
Mobile phase : 25 per cent V/V solution of ammonia R, water R,
ethyl acetate R, propanol R (5:10:40:40 V/V/V/V).
Application : 5 μL.
Development : over 2/3 of the plate.
Drying : at 50 °C for 20 min.
Detection : expose to iodine vapour for 30 min or until the
spots appear.
System suitability : reference solution :
– the chromatogram shows 2 clearly separated principal spots
due to impurity B (RF = 0.0) and thioctic acid (RF = about
0.3).
Limit :
– impurity B : any spot due to impurity B is not more intense
than the corresponding spot in the chromatogram obtained
with the reference solution (1.0 per cent).
Related substances. Liquid chromatography (2.2.29). Protect
the solutions from light.
Solvent mixture : a mixture of equal volumes of acetonitrile R1
and a 0.7 g/L solution of potassium dihydrogen phosphate R
previously adjusted to pH 3.6 with phosphoric acid R.
Test solution. Dissolve 50.0 mg of the substance to be
examined in the solvent mixture and dilute to 50.0 mL with
the solvent mixture.
Reference solution (a). Dissolve 5 mg of thioctic acid for system
suitability CRS (containing impurity A) in the solvent mixture
and dilute to 5 mL with the solvent mixture.
Reference solution (b). Dilute 1.0 mL of the test solution to
100.0 mL with the solvent mixture. Dilute 1.0 mL of this
solution to 10.0 mL with the solvent mixture.
Reference solution (c). Dissolve 50.0 mg of thioctic acid CRS
in the solvent mixture and dilute to 50.0 mL with the solvent
mixture.
Blank solution. Solvent mixture.
Column :
– size : l = 0.25 m, Ø = 4.6 mm ;
– stationary phase : octadecylsilyl silica gel for
chromatography R (5 μm) ;
– temperature : 35 °C.
Mobile phase : mix 8 volumes of acetonitrile R1, 41 volumes
of a 0.7 g/L solution of potassium dihydrogen phosphate R
previously adjusted to pH 3.0 with phosphoric acid R, and
51 volumes of methanol R.
Flow rate : 1.2 mL/min.
Detection : spectrophotometer at 215 nm.
Injection : 20 μL.
Run time : 2.5 times the retention time of thioctic acid.
Relative retention with reference to thioctic acid (retention
time = about 6 min) : impurity A = about 2.2.
System suitability :
– resolution : minimum 6.0 between the peaks due to thioctic
acid and impurity A in the chromatogram obtained with
reference solution (a) ;
General Notices (1) apply to all monographs and other texts
Thiomersal
– symmetry factor : maximum 2.0 for the peak due to
thioctic acid in the chromatogram obtained with reference
solution (c).
Limits :
– correction factor : for the calculation of content, multiply
the peak area of impurity A by 0.6 ;
– impurity A : not more than twice the area of the principal
peak in the chromatogram obtained with reference
solution (b) (0.2 per cent) ;
– unspecified impurities : for each impurity, not more than the
area of the principal peak in the chromatogram obtained
with reference solution (b) (0.10 per cent) ;
– total : not more than 3 times the area of the principal peak
in the chromatogram obtained with reference solution (b)
(0.3 per cent) ;
– disregard limit : 0.5 times the area of the principal peak in
the chromatogram obtained with reference solution (b)
(0.05 per cent).
Loss on drying (2.2.32) : maximum 0.2 per cent, determined
on 1.000 g by drying in vacuo at 40 °C for 3 h.
Sulfated ash (2.4.14): maximum 0.1 per cent, determined on
1.0 g.
ASSAY
Liquid chromatography (2.2.29) as described in the test for
related substances with the following modification.
Injection : test solution and reference solution (c).
Calculate the percentage content of C8H14O2S2 from the peak
areas and the declared content of thioctic acid CRS.
STORAGE
Protected from light.
IMPURITIES
Specified impurities : A, B.
A. 5-[(4RS)-1,2,3-trithian-4-yl]pentanoic acid,
B. α-hydro-ω-hydroxypoly[sulfanediyl(3-sulfanyl-8-
oxooctane-1,8-diyl)] (mixture of thioctic acid polymers).
01/2008:1625
corrected 10.0
THIOMERSAL
Thiomersalum
C9H9HgNaO2S Mr 404.8
[54-64-8]
DEFINITION
Sodium ethyl[2-sulfanylbenzoato(2-)-O,S]mercurate(1-).
Content : 97.0 per cent to 101.0 per cent (dried substance).
CHARACTERS
Appearance : white or almost white, crystalline powder.
4021