Sucralose 11-1005

Titrate the excess of sodium edetate with 0.1 M zinc sulfate Solubility
until the colour changes to pink. Freely soluble in water, soluble in anhydrous ethanol; slightly
1 mL of 0.1 JVI sodium edetate is equivalent to 2.698 mg of soluble in ethyl acetate.
AI. IDENTIFICATION
Sucrose octasulfate A. Specific optical rotation (see Tests).
Liquid chromatography (2.2.29) as described in the test for B. Infrared absorption spectrophotometry (2.2.24).
impurity A with the following modifications. Comparison sucralose CRS.
Mob£le phase 132 giL solution of ammonium sulfate R,
adjusted to pH 3.5 with phosphoric add R.
TESTS
Specific optical rotation (2.2.7)
Injection Test solution and reference solution (a).
+ 84.0 to + 87.5 (anhydrous substance).
Calculate the percentage content of C12H14035SS taking into
Dissolve 2.50 g in waterR and dilute to 25.0 mL with the
account the assigned content of potassium sucrose
same solvent.
octasulfate CRS and by multiplying the potassium sucrose
oetasulfate content by 0.757. Impurities H and I
Testsolution Dissolve 2.5 g of the substance to be examined
IMPURITIES in methanol R and dilute to 10.0 mL with the same solvent.
Specified impurities A.
Reference solution (a) Dissolve 1.0 g of mannitolR in waterR
and dilute to 10.0 mL with the same solvent.

ROb Reference solution (b) Dissolve 1.0 g of mannitol Rand

4.0 mg ofjructose R in waterR and dilute to 10.0 mL with
OR the same solvent.
__ RO
~

Plate TLC silica gelplateR.

:; __~O~RO
0 Appliauion 5!JL by applying the solution slowly in 1 !JL
RO aliquots and allowing the plate to dry between applications;
the 3 spots must be of a similar size.
OR
OR Detection Spray with a solution prepared as follows: dissolve
1.23 g of p-anisidine Rand 1.66 g of phthalic acid R in
R=S03H
100 mL of methanol R; store the solution in darkness and in
and H in a 7 to 1 ratio
a refrigerator to prevent it becoming discoloured; discard if
the solution becomes discoloured; heat the plate at
A. ~-D-fruetofuranosyl-Cl-D-glucopyranoside heptakis 100 ± 2 °C for 15 min and examine immediately against a
(hydrogensulfate) . dark background.
_ _ _ _--'- PhEur
System su£tab£l£ty The spot due to mannitol obtained with
reference solution (a) is colourless; darkening of the mannitol
spot indicates that the plate has been held for too long in the
oven and a 2 n d plate has to be prepared.
Sucralose Limit:
- sum of impurities H and I: any spot is not more intense
(Ph. Bur. monograph 2368)
than the spot due to fructose obtained with reference
solution (b) (0.1 per cent).

H;)-O, Related substances

Thin-layer chromatography (2.2.27).

\L.()O Test solution Dissolve 1.0 g of the substance to be examined

in methanolR and dilute to 10.0 mL with the same solvent.
CI\jOH Reference solution (a) Dilute 0.5 mL of the test solution to
HO 100.0 mL with methanol R.

OH
CI Reference solution (b) Dissolve the contents of a vial of
sucralose impurity B CRS in 1.0 mL of the test solution.
Plate TLC octadecylsilyl silica gelplate R.
397.6 56038-13-2 Mobzle phase acetonitrile R, 50 gIL solution of sodium
chloride R (30:70 V/V).
Action and use
Sweetening agent. Application 5 j.tL.
Development Over 3/4 of the plate.
PhEur '-- _
Drying In air.
DEFINITION Detection Spray with a 15 per cent V/V solution of sulfuric
1,6-Dichloro-l ,6-dideoxy-[3-o-fructofuranosyl 4-chloro-4- acid R in methanol R and heat at 125°C for 10 min.
deoxy-c-n-galactopyranoside,
Retardation factors Impurity A = about 0.3;
Content impurity B = about 0.35; sucralose = about 0.45;
98.0 per cent to 102.0 per cent (anhydrous substance). =
impurity F about 0.67; impurity G =
about 0.70;
CHARACTERS impurity E = about 0.72; impurity D = about 0.8.
Appearance System su£tab£l£ty Reference solution (b):
\Vh:ite or almost white, crystalline powder.

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11-1006 Sucralose 2020

";~o,
- the chromatogram shows 2 clearly separated spots due to
impurity B and sucralose.
Limits:
- impurities A, B;, D;, E;, F;, G: any spot, apart from the
principal spot, is not more intense than the spot in the ~ O
chromatogram obtained with reference solution (a) H°\§LoOH
HO
(0.5 per cent).
Water (2.5.12) cr
OH
Maximum 2.0 per cent, determined on 0.500 g.
Sulfated ash (2.4.14) D. l-chloro-l-deoxy-f-n-fructofuranosyl 4-chloro-4-deoxy-a.-
Maximum 0.7 per cent, determined on 1.0 g. D-galactopyranoside (1',4-dichloro-I',4-
ASSAY dideoxygalaetosucrose),
liquid chromatography (2.2.29).
Testsolution Dissolve 0.25 g of the substance to be
examined in the mobile phase and dilute to 25.0 mL with
the mobile phase.
"0-0,
Reference solution Dissolve 0.25 g of sucralose CRS in the
mobile phase and dilute to 25.0 mL with the mobile phase.
~
CI\§LoOH
O

Column: HO
- size: 1= 0.10 m, 0 = 4.6 mID;
- stationary phase: octadecylsilyl silica gelfor chromatography R OH
OH
(5 J.lIIl).
Mobile phase acetonitrile R, waterR (15:85 VIV). E. 6-ch1oro-6-deoxy-~-D-fructofuranosyl 4-chloro-4-deoxy-a.-
Flow rate 1.5 mUmin. D-galaetopyranoside (4,6'-dichloro-4,6'-
Detection Refractometer maintained at a constant dideoxygalactosucrose),
temperature.

"~~o,
Injection 20 ~.
Retention time Sucralose = about 3 min.
System suitability Reference solution:
- symmetryfactor: maximum 2.0 for the peak due to HN:.()
O
sucralose. Cl\§LoH
Calculate the percentage content of C12H19ChOs taking into HO
account the assigned content of sucralose CRS.
CI
IMPURITIES OH
Specified impurities A, B;, D;, E, F, G, H, 1.
F. I,6-dich1oro-I,6-dideoxy-~-D-fructofuranosyl c-o-

H3CyO.~
glucopyranoside (1',6'-dichloro-I ',6'-dideoxysucrose),
o CI 0
OH

O
CI\jOH
HO

CI
OH

A. 1,6-dichloro-I ,6-dideoXY-~-D-fructofuranosyl6-0-acetyl-4-
chloro-a-deoxy-c-o-galactopyranoside (6-0-
acetylsucralose), Ci. 3,6-anhydro-I-chIoro-I-deoXY-~-D-fruetofUranosyl
4-chIoro-4-deoxy-a.-D-galaetopyranoside (3',6'-anhydro-

CI~O
I',4-dichIoro-I',4-dideoxygalaetosucrose),

OH CI~OuJH
~
HO
O
CI\jOH I CI
HO OH

CI H. I,6-dichloro-l,6-dideoxy-~-D-fructofuranose,
OH

B. 1,6-dichloro-I ,6-dideoXY-~-D-fructofuranosyl6-chloro-6-
deoxy-a.-D-glucopyranoside (1',6,6'-trichloro-l ',6,6' -
trideoxysucrose),

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2020 Sucrose 11-1007

H:~O
of methanolR and dilute to 20 mL with the same mixture of
solvents.
OH Plate TLC silica gel G plateR.
OH Mobile phase cold saturated boric acid solution R,
OH 60 per cent VIV solution of glacial acetic acid R, anhydrous
ethanol R, acetone R, ethyl acetate R
1. 4-chIoro-4-deoxy-ex.-o-galactopyranose. (10:15:20:60:60 VIVIVIVIV).
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ PhEur Application 2 j.tL.
Development In an unsaturated tank, over 3/4 of the plate.
Drying In a current of warm air.
1 Detection Spray with a solution of 0.5 g of thymol R in a
Sucmse mixture of 5 mL of sulfuric acid R and 95 mL of ethanol
(96 per cent) R. Heat the plate at 130 "C for 10 min.
Refined Sugar
System suitability The chromatogram obtained with
(Ph. Eur. monograph 0204)
reference solution (b) shows 4 clearly separated spots.
Results The principal spot in the chromatogram obtained
HO~O with the test solution is similar in position, colour and size to
the principal spot in the chromatogram obtained with
OH
reference solution (a).
HO
e. Dilute 1 mL of solution S (see Tests) to 100 mL with
HO~OHO water R. To 5 mL of the solution add 0.15 mL of freshly
HO prepared copper sulfate solution Rand 2 mL of freshly
prepared dilute sodium hydroxide solution R. The solution is
OH
OH blue and clear and remains so after boiling. To the hot
solution add 4 mL of dilute hydrochloric acid R and boil for
342.3 57-50-1 1 min. Add 4 mL of dilute sodium hydroxide solution R.
An orange precipitate is formed immediately. +
Ae1ion and use
TESTS
Sweetening agent.
Soluv.u S
Preparation Dissolve 50.0 g in water R and dilute to 100 mL with the
Syrup same solvent.
PhEtr _ Appearance of solution
Solution S is clear (2.2.1).
DEFINITION
~-D-Fruetofuranosyl«-n-glucopyranoside.
Conductivity (2.2.38)
Maximum 35 IlS·cm-1 at 20 "C.
It contains no additives.
Dissolve 31.3 g in carbon dioxide-free water R prepared from
+CHARACTERS distilled water R and dilute to 100 mL with the same solvent.
Appearance Measure the conductivity of the solution (C 1), while gently
White or almost white, crystalline powder, or lustrous, stirring with a magnetic stirrer, and that of the water used for
colourless or white or almost white crystals. preparing the solution (Cz) . The readings must be stable
Solubility within 1 per cent over a period of 30 s. Calculate the
Very soluble in water, slightly soluble in ethanol conductivity of the solution of the substance to be examined
(96 per cent), practically insoluble in anhydrous ethanol. using the following expression:
IDENTIFICATION
First iiJemification: A.
Second identification: BJ C. Specific optical rotation (2.2.7)
A. Infrared absorption spectrophotometry (2.2.24). + 66.3 to + 67.0.
Comparison sucrose CRS. Dissolve 26.0 g in water R and dilute to 100.0 mL with the
B. Thin-layer chromatography (2.2.27). same solvent.
Test solution Dissolve 10 mg of the substance to be +Colour value
examined in a mixture of 2 volumes of water Rand Maximum 45.
3 volumes of methanolR and dilute to 20 mL with the same Dissolve 50.0 gin 50.0 mL of waterR. Mix, filter (diameter
mixture of solvents. of pores 0.45 urn) and degas. Measure the absorbance
Reference solution (a) Dissolve 10 mg of sucrose CRS in a (2.2.25) at 420 nm, using a minimum path length of 4 em (a
mixture of 2 volumes of water Rand 3 volumes of methanolR path length of 10 em or more is preferred).
and dilute to 20 mL with the same mixture of solvents. Calculate the colour value using the following expression:
Reference solution (b) Dissolve 10 mg ofjructose R, 10 mg of
A x 1000
glucose R, 10 mg of lactose monohydrate Rand 10 mg of
sucrose R in a mixture of 2 volumes of water Rand 3 volumes b x c

1 This monograph has undergone pharmacopoeial harmonisation.

See chapter 5.8 Pharmacopoeial harmonisation.

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