PMID- 18513910
OWN - NLM
STAT- MEDLINE
DCOM- 20081203
LR  - 20080908
IS  - 0731-7085 (Print)
IS  - 0731-7085 (Linking)
VI  - 48
IP  - 2
DP  - 2008 Sep 29
TI  - New method for low molecular weight heparin quantification in tablets by 
      suppressed conductivity detection and cryptand column.
PG  - 467-71
LID - 10.1016/j.jpba.2008.04.009 [doi]
AB  - Unfractioned Heparins (UFH) and Low Molecular Weight Heparins (LMWHs) are 
      non-chromophoric, high charged sulphated molecules which are difficult to elute 
      and detect with conventional liquid chromatography methods. Moreover, the 
      detection of LMWHs at low concentration level, like in samples coming from 
      dissolution test of tablets formulated with Heparins is problematic due to the 
      weak response by UV or refractive index detection. According to the European 
      Pharmacopoeia requirements, the assay of LMWHs is based on the anti-Xa activity 
      and anti-IIa activity factors, which are biological parameters related to the 
      antithrombotic activity of this compound family. The same assay method could also 
      be applied to determine the dissolution rate of LMWHs contained in tablets, but 
      it is time consuming and expensive test. The challenge was to develop a simpler 
      and faster alternative method based on Ion Chromatography coupled with Suppressed 
      Conductivity detection, but the particular polycharge interaction of LMWHs with 
      anions exchanger makes the analyte with standard eluents and columns difficult to 
      elute . The analytical problem could be solved by using a particular 
      chromatographic phase with 2,2,2 cryptand sites which gives variable capacity in 
      anion exchange depending on the used eluent. Such phase was very effective for 
      the elution of strongly retained polyanions using simple inorganic eluent phase 
      suitable for suppressed conductivity detection as well. The developed method 
      allows the elution of a unique peak, which represents the whole polymeric 
      distribution, and therefore it makes easy to quantify quickly and selectively the 
      active ingredient in case of multiple analysis like when a dissolution test is 
      required to characterize and discriminate between different tablets formulations. 
      The method was tested and developed in Cosmo Pharmaceuticals QC labs and the 
      validation results are reported in the present paper. Besides, a comparison 
      between biological and chromatographic methods was carried out as well.
FAU - Abballe, F
AU  - Abballe F
AD  - Dionex Srl, via XXV Aprile, San Donato Milanese, MI, Italy.
FAU - Lombardi, M
AU  - Lombardi M
FAU - Maccone, I
AU  - Maccone I
FAU - Palazzo, G
AU  - Palazzo G
FAU - Severoni, A
AU  - Severoni A
FAU - Travaini, S
AU  - Travaini S
FAU - Venturini, A
AU  - Venturini A
LA  - eng
PT  - Journal Article
DEP - 20080415
PL  - England
TA  - J Pharm Biomed Anal
JT  - Journal of pharmaceutical and biomedical analysis
JID - 8309336
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 0 (Tablets)
SB  - IM
MH  - Chromatography/*methods
MH  - Electric Conductivity
MH  - Heparin, Low-Molecular-Weight/*analysis
MH  - Tablets
EDAT- 2008/06/03 09:00
MHDA- 2008/12/17 09:00
CRDT- 2008/06/03 09:00
PHST- 2007/11/13 00:00 [received]
PHST- 2008/04/05 00:00 [revised]
PHST- 2008/04/07 00:00 [accepted]
PHST- 2008/06/03 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2008/06/03 09:00 [entrez]
AID - S0731-7085(08)00216-1 [pii]
AID - 10.1016/j.jpba.2008.04.009 [doi]
PST - ppublish
SO  - J Pharm Biomed Anal. 2008 Sep 29;48(2):467-71. doi: 10.1016/j.jpba.2008.04.009. 
      Epub 2008 Apr 15.