PMID- 32004766
OWN - NLM
STAT- MEDLINE
DCOM- 20201204
LR  - 20201214
IS  - 1873-264X (Electronic)
IS  - 0731-7085 (Linking)
VI  - 182
DP  - 2020 Apr 15
TI  - Characterization of therapeutic oligonucleotides by liquid chromatography.
PG  - 113105
LID - S0731-7085(19)32877-8 [pii]
LID - 10.1016/j.jpba.2020.113105 [doi]
AB  - Marketed therapies in the pharmaceutical landscape are rapidly evolving and 
      getting more diverse. Small molecule medicines have dominated in the past while 
      antibodies have grown dramatically in recent years. However, the failure of 
      traditional small and large molecules in accessing certain targets has led to 
      increased R&D efforts to develop alternative modalities. Therapeutic 
      oligonucleotides (ONs) can accurately be directed against their ribonucleic acid 
      (RNA) target and represent a promising approach in previously untreated diseases. 
      Established automated synthesis of ONs coupled with chemical improvements and the 
      advance of new drug delivery technologies has recently brought ONs to a 
      heightened level of interest. The first part of the present review describes the 
      different classes of oligonucleotides, namely antisense oligonucleotide (ASO), 
      small interfering RNA (siRNA), microRNA (miRNA), aptamer and immunostimulatory 
      ON, with a focus on their delivery systems relevant for future analytical 
      characterization. The second part reviews the typical impurities in therapeutic 
      ON products. The third part discusses the use of historical methods anion 
      exchange chromatography (AEX), ion-pair reversed phase liquid chromatography 
      (IP-RP), mixed-mode chromatography (MMC) and recent analytical methodologies of 
      hydrophilic interaction liquid chromatography (HILIC), two-dimensional liquid 
      chromatography (2D-LC) mass spectrometry for the characterization of ASO and 
      siRNA modalities. The effects of physicochemical properties of RPLC columns and 
      ion-pair agents on ON separation are specifically addressed with possible future 
      directions for method development provided. Finally, some innovative analytical 
      developments for the analysis of siRNAs and their delivery materials to pave the 
      way toward the use of multi-attribute methods in the near future are discussed.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Goyon, Alexandre
AU  - Goyon A
AD  - Small Molecules Pharmaceutical Sciences, Genentech Inc., 1 DNA Way, South San 
      Francisco, CA 94080, USA.
FAU - Yehl, Peter
AU  - Yehl P
AD  - Small Molecules Pharmaceutical Sciences, Genentech Inc., 1 DNA Way, South San 
      Francisco, CA 94080, USA.
FAU - Zhang, Kelly
AU  - Zhang K
AD  - Small Molecules Pharmaceutical Sciences, Genentech Inc., 1 DNA Way, South San 
      Francisco, CA 94080, USA. Electronic address: zhang.kelly@gene.com.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20200120
PL  - England
TA  - J Pharm Biomed Anal
JT  - Journal of pharmaceutical and biomedical analysis
JID - 8309336
RN  - 0 (Oligonucleotides)
RN  - 0 (RNA, Small Interfering)
SB  - IM
MH  - Chromatography, Liquid/*methods
MH  - Drug Contamination
MH  - *Drug Delivery Systems
MH  - Humans
MH  - Oligonucleotides/administration & dosage/*analysis
MH  - RNA, Small Interfering/administration & dosage/analysis
OTO - NOTNLM
OT  - 2D-LC
OT  - AEX
OT  - HILIC
OT  - Ion-pair RPLC
OT  - MMC
OT  - Oligonucleotides
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2020/02/01 06:00
MHDA- 2020/12/15 06:00
CRDT- 2020/02/01 06:00
PHST- 2019/11/26 00:00 [received]
PHST- 2019/12/21 00:00 [revised]
PHST- 2020/01/08 00:00 [accepted]
PHST- 2020/02/01 06:00 [pubmed]
PHST- 2020/12/15 06:00 [medline]
PHST- 2020/02/01 06:00 [entrez]
AID - S0731-7085(19)32877-8 [pii]
AID - 10.1016/j.jpba.2020.113105 [doi]
PST - ppublish
SO  - J Pharm Biomed Anal. 2020 Apr 15;182:113105. doi: 10.1016/j.jpba.2020.113105. 
      Epub 2020 Jan 20.