PMID- 30055911
OWN - NLM
STAT- MEDLINE
DCOM- 20180919
LR  - 20181004
IS  - 1873-3778 (Electronic)
IS  - 0021-9673 (Linking)
VI  - 1569
DP  - 2018 Sep 28
TI  - Qualitative and quantitative analysis of 2, 5-anhydro-d-mannitol in low molecular 
      weight heparins with high performance anion exchange chromatography hyphenated 
      quadrupole time of flight mass spectrometry.
PG  - 160-167
LID - S0021-9673(18)30942-7 [pii]
LID - 10.1016/j.chroma.2018.07.058 [doi]
AB  - Low molecular weight heparins (LMWHs), derived from unfractionated heparin (UFH) 
      by chemical or enzymatic degradation, have lower side effects than that of 
      heparin. Enoxaparin, nadroparin, and dalteparin are the most widely used LMWHs. 
      Nadroparin and dalteparin are prepared through nitrous acid degradation followed 
      by a subsequent reduction process, in which specific residue, 
      2,5-anhydro-d-mannitol (An-Man), is formed at the reducing terminals of generated 
      sugar chains. However, few practicable analytical method was available to analyze 
      An-Man qualitatively and quantitatively. In this work, a HPAEC-PAD-MS method was 
      developed to analyze monosaccharides in heparin and LMWHs, especially An-Man. An 
      ion suppressor is set up between HPAEC and MS to remove the nonvolatile salts 
      from HPAEC and make the elute compatible to MS. Various monosaccharides were 
      separated well with HPAEC. Online MS and MS/MS confirmed all sugar residues in 
      the hydrolysates of heparin samples. The specific residue, An-Man, was only 
      observed in the hydrolysates of LMWHs prepared with nitrous acid degradation and 
      reduction. In addition, major glucosamine and minor arabinose/galactose were 
      observed in all heparin samples. The amounts of these sugar residues were 
      quantitated with PAD, simultaneously. The ratio of glucosamine to An-Man could be 
      used to calculate the molecular weight of LMWHs. The calculated values are 
      comparable to the value measured with size-exclusion chromatography-multiple 
      angle laser scattering detection. Higher the ratio of glucosamine to An-Man 
      higher the molecular weight. The HPAEC-PAD-MS platform is an accurate, precise 
      and efficient way to identify LMWHs by determination of An-Man. It is also an 
      alternative method to detect the MWs of LMWHs having An-Man for quality control 
      purposes.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Yi, Lin
AU  - Yi L
AD  - Jiangsu Key Laboratory of Translational Research and Therapy for 
      Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, 
      Suzhou, Jiangsu, 215021, China.
FAU - Zhang, Qinghua
AU  - Zhang Q
AD  - Tianjin Chase Sun Pharmaceutical Co. LTD, Tianjin, 300111, China.
FAU - Meng, Yao
AU  - Meng Y
AD  - Jiangsu Key Laboratory of Translational Research and Therapy for 
      Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, 
      Suzhou, Jiangsu, 215021, China.
FAU - Hao, Jie
AU  - Hao J
AD  - Jiangsu Key Laboratory of Translational Research and Therapy for 
      Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, 
      Suzhou, Jiangsu, 215021, China.
FAU - Xie, Bingying
AU  - Xie B
AD  - Jiangsu Key Laboratory of Translational Research and Therapy for 
      Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, 
      Suzhou, Jiangsu, 215021, China.
FAU - Gan, Hao
AU  - Gan H
AD  - Tianjin Chase Sun Pharmaceutical Co. LTD, Tianjin, 300111, China.
FAU - Li, Duxin
AU  - Li D
AD  - Jiangsu Key Laboratory of Translational Research and Therapy for 
      Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, 
      Suzhou, Jiangsu, 215021, China.
FAU - Dong, Kai
AU  - Dong K
AD  - Tianjin Chase Sun Pharmaceutical Co. LTD, Tianjin, 300111, China. Electronic 
      address: dbqay@sina.com.
FAU - Zhang, Zhenqing
AU  - Zhang Z
AD  - Jiangsu Key Laboratory of Translational Research and Therapy for 
      Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, 
      Suzhou, Jiangsu, 215021, China. Electronic address: z_zhang@suda.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20180723
PL  - Netherlands
TA  - J Chromatogr A
JT  - Journal of chromatography. A
JID - 9318488
RN  - 0 (Anions)
RN  - 0 (Enoxaparin)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 0 (Monosaccharides)
RN  - 0 (Nadroparin)
RN  - 3OWL53L36A (Mannitol)
SB  - IM
MH  - Anions
MH  - Chromatography, Ion Exchange/*methods
MH  - Enoxaparin/chemistry
MH  - Heparin, Low-Molecular-Weight/*chemistry
MH  - Humans
MH  - Hydrolysis
MH  - Mannitol/*analysis
MH  - Molecular Weight
MH  - Monosaccharides/analysis
MH  - Nadroparin/chemistry
MH  - Reference Standards
MH  - Tandem Mass Spectrometry/*methods
OTO - NOTNLM
OT  - 2,5-Anhydro-manitol
OT  - HPAEC-PAD-MS
OT  - Heparin
OT  - Low molecular weight heparin
OT  - Monosaccharide composition
OT  - Nadroparin
EDAT- 2018/07/30 06:00
MHDA- 2018/09/20 06:00
CRDT- 2018/07/30 06:00
PHST- 2018/05/14 00:00 [received]
PHST- 2018/07/12 00:00 [revised]
PHST- 2018/07/22 00:00 [accepted]
PHST- 2018/07/30 06:00 [pubmed]
PHST- 2018/09/20 06:00 [medline]
PHST- 2018/07/30 06:00 [entrez]
AID - S0021-9673(18)30942-7 [pii]
AID - 10.1016/j.chroma.2018.07.058 [doi]
PST - ppublish
SO  - J Chromatogr A. 2018 Sep 28;1569:160-167. doi: 10.1016/j.chroma.2018.07.058. Epub 
      2018 Jul 23.