PMID- 33684830
OWN - NLM
STAT- MEDLINE
DCOM- 20210617
LR  - 20210617
IS  - 1873-264X (Electronic)
IS  - 0731-7085 (Linking)
VI  - 198
DP  - 2021 May 10
TI  - Selective quantitation of B(2)Pin(2) and B(2)(OH)(4) in active pharmaceutical 
      ingredients by gas chromatography- mass spectrometry.
PG  - 113987
LID - S0731-7085(21)00099-6 [pii]
LID - 10.1016/j.jpba.2021.113987 [doi]
AB  - This paper describes a sensitive and selective method for the simultaneous 
      determination of bispinacolato diboron (B(2)Pin(2)) and tetrahydroxy diboron 
      (B(2)(OH)(4)) in a small molecule Active Pharmaceutical Ingredient (API) by gas 
      chromatography - mass spectrometry (GC-MS). These reagents are commonly used in 
      the Suzuki-Miyaura coupling reaction and analytical methods are typically 
      required to monitor these reagents at the Threshold of Toxicological Concern 
      (TTC) level since they are Class II impurities based on ICH M7 guideline. In this 
      study, hexylene glycol was added to derivatize B(2)(OH)(4) before direct 
      injection to the GC-MS, and B(2)Pin(2) is analyzed in the same analysis without 
      derivatization. Under the optimal conditions, the limit of detection (LOD) and 
      the limit of quantitation (LOQ) were 65 ng/mL and 130 ng/mL respectively. Average 
      recoveries of the analytes spiked in the drug substance at the 13 ppm (LOQ) and 
      104 ppm (TTC) levels were in the range of 77.9 %-85.3 % with relative standard 
      deviations (RSDs) of 2.8 %-6.8 %. The linearity for both analytes was established 
      in the range of 0.130-2.080 mug/mL with a correlation coefficient (r) of 0.9998 
      and the derivatization reaction is very rapid and complete within 15 minutes.
CI  - Copyright (c) 2021. Published by Elsevier B.V.
FAU - Shamirian, Armen
AU  - Shamirian A
AD  - Gilead Sciences, 333 Lakeside Drive, Foster city, CA, 94404, United States.
FAU - Foti, Christopher
AU  - Foti C
AD  - Gilead Sciences, 333 Lakeside Drive, Foster city, CA, 94404, United States. 
      Electronic address: chris.foti@gilead.com.
FAU - Mitchell, Scott S
AU  - Mitchell SS
AD  - Gilead Sciences, 333 Lakeside Drive, Foster city, CA, 94404, United States.
LA  - eng
PT  - Journal Article
DEP - 20210223
PL  - England
TA  - J Pharm Biomed Anal
JT  - Journal of pharmaceutical and biomedical analysis
JID - 8309336
RN  - 0 (Indicators and Reagents)
RN  - 0 (Pharmaceutical Preparations)
SB  - IM
MH  - Gas Chromatography-Mass Spectrometry
MH  - Indicators and Reagents
MH  - Limit of Detection
MH  - *Pharmaceutical Preparations
OTO - NOTNLM
OT  - Analytical chemistry
OT  - Bis(pinacolato)diboron
OT  - Chromatography
OT  - Derivatization
OT  - Gas chromatography-mass spectrometry
OT  - Mass spectrometry
OT  - Mutagenic impurities
OT  - Structure
OT  - Tetrahydroxydiboron
OT  - Toxicology
COIS- Declaration of Competing Interest The Authors declare that there is no conflict 
      of interest.
EDAT- 2021/03/09 06:00
MHDA- 2021/06/22 06:00
CRDT- 2021/03/08 20:17
PHST- 2020/12/11 00:00 [received]
PHST- 2021/02/17 00:00 [revised]
PHST- 2021/02/19 00:00 [accepted]
PHST- 2021/03/09 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2021/03/08 20:17 [entrez]
AID - S0731-7085(21)00099-6 [pii]
AID - 10.1016/j.jpba.2021.113987 [doi]
PST - ppublish
SO  - J Pharm Biomed Anal. 2021 May 10;198:113987. doi: 10.1016/j.jpba.2021.113987. 
      Epub 2021 Feb 23.