Test |
Method |
Range |
Appearance
Visual
white or off-white powder
Identification A
IR (USP <197>, EP 2.2.24)
complies with SBECD reference
Identification B
HPLC (USP <621>, EP 2.2.29)
tR of major peak complies with SBECD reference
Identification C
CE (USP <1053>, EP 2.2.47)
Average Degree of Substitution: 6.2 - 6.9
Identification D
Sodium ID (USP <191>, EP 2.3.1)
positive test
Assay
HPLC (USP <621>, EP 2.2.29)
95.0 - 105.0% on the anhydrous basis
Heavy metals
ICP-MS (USP <232, 233>
Cadmium NMT 0.5 µg/g
Lead NMT 0.5 µg/g
Arsenic NMT 1.5 µg/g
Mercury NMT 3.0 µg/g
Chromium NMT 110 µg/g
Nickel NMT 2 µg/g
Molybdenium NMT 150 µg/g
Vanadium NMT 1 µg/g
Limit of related substances
beta-cyclodextrin (Betadex)
total other impurities
HPLC (USP <621>, EP 2.2.29)
NMT 0.1%
NMT 1.0%
Limit of 1,4-Butane Sultone
GC (USP <621>, EP 2.2.28)
NMT 0.5 ppm
Limit of Sodium Chloride
Limit test (USP <221>)
NMT 0.2%
Limit of 4-Hydroxybutane-1-sulfonic Acid
CE (USP <1053>, EP 2.2.47)
NMT 0.09%
Limit of Bis(4-sulfobutyl) Ether Disodium
CE (USP <1053>, EP 2.2.47)
NMT 0.05%
Bacterial Endotoxin Test
EP-USP harmonized method
≤ 24 IU/g
Microbial Enumeration Tests
EP-USP harmonized method
TAMC ≤ 100 cfu/g
TYMC ≤ 50 cfu/g
Test for Specified Microorganism
EP-USP harmonized method
absence of Escherichia Coli /1 g
Phosphate content
UV-Vis Spectroscopy (USP <851>, EP 2.2.25)
525-700 μg/g
Clarity of solution (30%, w/v)
Visual, see details in the USP Monograph, EP 2.2.1
the solution is clear, and essentially free from particles of foreign matter
Average Degree of Substitution (n)
CE (USP <1053>, EP 2.2.47)
6.2 - 6.9
Peak distribution
CE (USP <1053>, EP 2.2.47)
each SBECD peak (I-X) meets the limit range (peak area %) of the Monograph
SBECD sodium Limit range
peaks (% peak area)
I (DS-1) 0 - 0.3
II (DS-2) 0 - 0.9
III (DS-3) 0.5 - 5.0
IV (DS-4) 2.0 - 10.0
V (DS-5) 10.0 - 20.0
VI (DS-6) 15.0 - 25.0
VII (DS-7) 20.0 - 30.0
VII (DS-8) 10.0 - 25.0
IX (DS-9) 2.0 - 12.0
X (DS-10) 0 - 4.0
Residual solvents: ethanol
GC (USP <621>, EP 2.2.28)
NMT 2500 ppm
pH (30%, w/V)
USP <791>
4.0 - 6.8
Water content
USP <921> Method I, EP 2.5.12
NMT 10.0 %