|
Product name
|
Gemcitabine hydrochloride
|
|
Molecular Formula
|
C9H12ClF2N3O4
|
|
Molecular Weight
|
299.66
|
|
CAS No.
|
122111-03-9
|
|
Quality Standard
|
EP / USP,
medical grade
|
|
Appearance
|
White powder
|
|
COA of Gemcitabine Hydrochloride
|
Test
|
Specification
|
Result
|
|
Characters
|
White or
almost white powder
|
Conform
|
|
Identification
|
The IR
spectrum of sample is concordant with the IR spectrum of Gemcitabine
hydrochloride reference standard.
|
Conform
|
|
Chloride
|
Conform
|
|
Solubility
|
Soluble in
water; sparingly soluble in methanol, practically insoluble in alchohol and
in polar organic solvents
|
Conform
|
|
pH
|
2.0 to 3.0
|
2.2
|
|
Specific
rotation
|
+43° to +50°
|
+49°
|
|
Heavy metals
|
Not more than
10ppm
|
<10ppm
|
|
Residue on
ignition
|
Not more than
0.1%
|
0.06%
|
|
Related
substances
|
Cytosine: not
more than 0.1%
|
0.02%
|
|
α-anomer: not
more than 0.1%
|
Not detected
|
|
Any other
impurity: not more than 0.1%
|
0.04%
|
|
Total impurities:
not more than 0.2%
|
0.10%
|
|
Bacterial
endotoxins
|
Not more than
0.05 EU/mg
|
<0.05 EU/mg
|
|
bacteria
|
Not more than
100 CUFU/g
|
<10 CFU/g
|
|
Yeasts & Moulds
|
Not more than
20 CFU/g
|
<10 CFU/g
|
|
Escherichia coli
|
Not detected
|
Not detected
|
|
Residual
solvents
|
Methanol: not
more than 0.3%
|
0.0001%
|
|
Acetone: not
more than 0.5%
|
0.16%
|
|
Isopropyl
alcohol: not more than 0.5%
|
Not detected
|
|
Ethylene
Dichloride: not more than 5ppm
|
Not detected
|
|
Assay
|
97.5% to
101.5% ( on as-is basis)
|
99.4%
|
|
Conclusion
|
Conforms to
USP34.
|
|
Function of Gemcitabine hydrochloride
As a prodrug, gemcitabine hydrochloride is a good substrate for phosphorylation
of deoxythymidine kinase in the cell
and is converted into the following metabolites under the action of enzymes:
gemcitabine monophosphate (dFdCMP), gemcitabine diphosphate (dFdCDP) and
gemcitabine Phosphate (dFdCTP) dFdCDP and dFdCTP are active products. dFdCDP
inhibits ribonucleotide reductase, thereby reducing the amount of
deoxynucleotides required for repair of DNA synthesis (especially dCTP). Low
levels of dCTP reverse the normal negative feedback inhibition of
deoxyglycoside kinase, resulting in more dFdCTP Accumulation. At the same time,
dFdCDP inhibits the deamination effect of dCTP-induced deoxycytidine on dFdCMP,
and dFdCTP directly inhibits deoxycytidine deaminase, thereby converting more
dFdCMP into the active metabolite dFdCMP deamination, and dFdCTP directly
inhibits deoxygenation Cytidine deaminase, which converts more dFdCMP into the
active metabolite dFdCDP, dFd-CTP and dFdCTP competes with dCTP for binding
into the DNA strand, inserting it into the deoxycytidine site in the DNA
strand, and allowing guanosine to interact with it After pairing, the
gemcitabine molecule is "masked" by this guanosine to prevent it from
being removed and repaired by exonuclease, and then DNA strand synthesis stops,
and DNA breaks and the cell dies.
