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D-glucose, polymer with xylitol

Compositional Guideline for D-glucose, polymer with xylitol permitted for use in listed medicines.

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Description 

D-glucose, polymer with xylitol is the product of chemical glycosylation between xylitol and D-glucose in the presence of a mineral acid catalyst. The reaction mixture is then neutralised and diluted to yield an inseparable mixture comprising of xylitylglucoside (CAS No: 1095751-96-4), anhydroxylitol (CAS No: 53448-53-6), xylitol (CAS No: 87-99-0), and D-glucose (CAS No: 50-99-7).

CAS number: 875800-11-6

Molecular structures:

Xylitylglucoside:

Xylitylglucoside

Anhydroxylitol:

Anhydroxylitol

Xylitol:

Xylitol

D-glucose:

D-glucose

Test

Method reference

Acceptance criteria

Characterisation 
General properties
Appearance

Visual

Transparent to slightly opalescent yellowish liquid
pH

Ph. Eur. 2.2.3

4.5 - 7.0
Water content

Karl Fischer (Ph. Eur. 2.5.12)

15 - 17%
Boiling point 

Ph. Eur. 2.2.12 

314.9 ± 2.6°C
Density 

USP <699> 

1435 Kg/m3 at 20°C
Water solubility 

Commission Directive 92/69/EEC (1992) - Flask Method A6 

674 g/L at 20°C
Identity
LC-MS

LC-MS[1]

Detection of molecular ions peaks for all components as follows:

  • m/z 319 [M+23] for monoether xylitylglucoside 
  • m/z 481 [M+23] for diether xylitylglucoside
  • m/z 175 [M+23] for xylitol
  • m/z 327 [2M+23] for xylitol dimer
  • m/z 157 [M+23] for 1,4-anhydroxylitol 
  • m/z 291 [2M+23] for 1,4-anhydroxylitol dimer

GC

 

GC[2]

Observation of peaks at retention times:

  • 11 min (xylitan);
  • 14 min (xylitol);
  • 16 min (α-D-glucose);
  • 17 min (β-D-glucose);
  • 22-26 min (xylitylglucosides dimers);
  • 30-34 min (xylitylglucosides trimers);
  • 36-38 min (xylitylglucosides tetramers)
FT-IR

FT-IR[3]

Observation of characteristic peaks at 3329, 2936, 1418, 1260, 1040, and 823 cm-1.
NMR

USP <761> 

1H-NMR: Observation of signals at 3.2-4.7 ppm.

13C-NMR: Observation of signals at 68-94 ppm.

DEPT-135: Observation of signals at 72.6 ppm and 60.0-62.0 ppm in DEPT-135 sub-spectra.

UV-Vis 

USP <857>

Observation of a single absorption peak at 195 nm.
Assay

Hydroxyl value on dry material 

 

USP <401>

Limits for the assay test:

1100 - 1300 mg KOH/g

GC

 

GC[2]

Xylitylglycoside (35-50%);

Anhydroxylitol (24-34%);

Xylitol (5-15%);

D-glucose (0-5%)

Impurities and incidental constituents 
Elemental impurities
LeadICP-MS[4]<2.00 ppm
CadmiumICP-MS[4]<0.10 ppm
MercuryICP-MS[4]<0.10 ppm 
ArsenicICP-MS[4]<0.50 ppm
NickelICP-MS[4]<2.00 ppm
ChromiumICP-MS[4]<1.00 ppm
CobaltICP-MS[4]<2.00 ppm
Antimony ICP-MS[4]<0.50 ppm
Microbiology  
While substance manufacturers are encouraged to include limits for objectionable microorganisms, it is the product into which those substances are formulated that is subject to a legally binding set of criteria. The Therapeutic Goods Order No. 100 'Microbiological Standards for Medicines' mandates that any finished product that contains the ingredient, alone or in combination with other ingredients, must comply with the microbial acceptance criteria set by Clause 11 of the Order.

Footnotes

  1. LC-MS: LC system: Acquity UPLC I-Class; Column: Acquity BEH Amide 50 x 2.1 mm; 1.7 µm particle size; Solvent wash: Water/MeOH; Solvent purge: Water/Acetonitrile. Gradient: A: Acetonitrile/Water (80:20) + 1% NH4OH; B: Acetonitrile/Water (30:70) + 1% NH4OH; HR-MS system: Xevo G2-XS ToF (Waters); Mode of ionisation: ESI; m/z and calibration mode: 50 to 1200 m/z. 
  2. GC: Column: Varian fused silica CP-Wax-52CB (10 m x 0.10 mm id, DF 0.2, cat no. CP7335); Injection volume: 5.0 μL; Helium carrier gas: 4 psi at room temperature; Flame ionization detector; Detection temperature: 350°C (8°C/min); Solvent plug: 10 µL; Injector temperature: 300°C; Make-up gas: air and hydrogen; Leak: 60 mL/min. 
  3. FT-IR: Nicolet IS10 IR spectrophotometer with ATR window (mono-reflexion); wave number range of 400 to 4,000 cm-1, minimum 32 scans, and 4.00 cm-1 resolution.
  4. ICP-MS: Samples dilution factor 100 as follows: 0.30 g of sample + 0.30 g of internal standard solution (In and Re at 5 ppm) + 0.45 mL of concentrated HNO3 + 0.15 mL of concentrated HCl + complete to 30 g with ultrapure water. Standard solutions of Ag, Al, As, B, Ba, Be, Bi, Ca, Cd, Co, Cr, Cs, Cu, Fe, Ga, Ge, Hf, In, K, Li, Mg, Mn, Mo, Na, Nb, Ni, Pb, Rb, Sb, Se, Sn, Sr, Ta, Ti, Tl, V, W, Zn, Zr at 5 ppb, 10 ppb, and 50 ppb.

Abbreviations

CAS: Chemical abstract services

DEPT: Distortionless Enhancement by Polarisation Transfer

FT-IR: Fourier-transform infrared spectroscopy

GC: Gas chromatography

ICP-MS: Inductively coupled plasma - Mass spectrometry

LC-MS: Liquid chromatography - Mass spectrometry

NMR: Nuclear magnetic resonance spectroscopy

Ph. Eur.: European Pharmacopoeia

USP: United States Pharmacopeia

UV-Vis: Ultraviolet-visible spectroscopy

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