Trace impurities identified by HPLC/Electrospray MS in two different synthetic batches of 4-boronophenylalanine

Jyrki Vähätalo (Corresponding Author), Jari Tuominen, Juha Kokkonen, O. Kris, S.-L. Karonen, M. Kallio

Research output: Contribution to journalArticleScientificpeer-review

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Abstract

The chemical purity of two synthetic 4‐boronophenylalanine (BPA, C9H12O4BN) batches produced by two different pathways were investigated by high performance liquid chromatography/electrospray mass spectrometry.
Currently, BPA is one of the most important clinical boron carriers in boron neutron capture therapy (BNCT). Low energy tandem mass spectrometry was used to elucidate the structure of BPA and two minor signals eluting later than the major compound. In the mass spectrom a very intense singly charged [M+H]+ ion m/z 209 was observed. The ratio of 10B/11B was estimated also.
The product‐ion spectrum of BPA shows distinct losses of 18, 46 and 89 u. Based on the fragmentation of the major compound two impurities were characterized. In both cases an intense molecular ion, 244 u and 285 u was observed.
Knowing the synthetic pathway and fragmentation of the major compound we suggest the following formulae for the impurities: C9H10O2BrN and C15H16O4BN. Further evidence to the first impurity is the detected isotope pattern, corresponding to bromine. The existence of the impurities can be explained and avoided by exploring the synthetic pathways used.
High performance liquid chromatography/electrospray mass spectrometry was demonstrated to be an important novel analytical instrument to check the purity of BPA prior to clinical studies in BNCT.
Original languageEnglish
Pages (from-to)1118-1122
JournalRapid Communications in Mass Spectrometry
Volume12
Issue number16
DOIs
Publication statusPublished - 1998
MoE publication typeA1 Journal article-refereed

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Boron
Impurities
Mass spectrometry
High performance liquid chromatography
Neutrons
Ions
Bromine
Isotopes
4-boronophenylalanine

Cite this

Vähätalo, Jyrki ; Tuominen, Jari ; Kokkonen, Juha ; Kris, O. ; Karonen, S.-L. ; Kallio, M. / Trace impurities identified by HPLC/Electrospray MS in two different synthetic batches of 4-boronophenylalanine. In: Rapid Communications in Mass Spectrometry. 1998 ; Vol. 12, No. 16. pp. 1118-1122.
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abstract = "The chemical purity of two synthetic 4‐boronophenylalanine (BPA, C9H12O4BN) batches produced by two different pathways were investigated by high performance liquid chromatography/electrospray mass spectrometry. Currently, BPA is one of the most important clinical boron carriers in boron neutron capture therapy (BNCT). Low energy tandem mass spectrometry was used to elucidate the structure of BPA and two minor signals eluting later than the major compound. In the mass spectrom a very intense singly charged [M+H]+ ion m/z 209 was observed. The ratio of 10B/11B was estimated also. The product‐ion spectrum of BPA shows distinct losses of 18, 46 and 89 u. Based on the fragmentation of the major compound two impurities were characterized. In both cases an intense molecular ion, 244 u and 285 u was observed. Knowing the synthetic pathway and fragmentation of the major compound we suggest the following formulae for the impurities: C9H10O2BrN and C15H16O4BN. Further evidence to the first impurity is the detected isotope pattern, corresponding to bromine. The existence of the impurities can be explained and avoided by exploring the synthetic pathways used. High performance liquid chromatography/electrospray mass spectrometry was demonstrated to be an important novel analytical instrument to check the purity of BPA prior to clinical studies in BNCT.",
author = "Jyrki V{\"a}h{\"a}talo and Jari Tuominen and Juha Kokkonen and O. Kris and S.-L. Karonen and M. Kallio",
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Trace impurities identified by HPLC/Electrospray MS in two different synthetic batches of 4-boronophenylalanine. / Vähätalo, Jyrki (Corresponding Author); Tuominen, Jari; Kokkonen, Juha; Kris, O.; Karonen, S.-L.; Kallio, M.

In: Rapid Communications in Mass Spectrometry, Vol. 12, No. 16, 1998, p. 1118-1122.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Trace impurities identified by HPLC/Electrospray MS in two different synthetic batches of 4-boronophenylalanine

AU - Vähätalo, Jyrki

AU - Tuominen, Jari

AU - Kokkonen, Juha

AU - Kris, O.

AU - Karonen, S.-L.

AU - Kallio, M.

PY - 1998

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N2 - The chemical purity of two synthetic 4‐boronophenylalanine (BPA, C9H12O4BN) batches produced by two different pathways were investigated by high performance liquid chromatography/electrospray mass spectrometry. Currently, BPA is one of the most important clinical boron carriers in boron neutron capture therapy (BNCT). Low energy tandem mass spectrometry was used to elucidate the structure of BPA and two minor signals eluting later than the major compound. In the mass spectrom a very intense singly charged [M+H]+ ion m/z 209 was observed. The ratio of 10B/11B was estimated also. The product‐ion spectrum of BPA shows distinct losses of 18, 46 and 89 u. Based on the fragmentation of the major compound two impurities were characterized. In both cases an intense molecular ion, 244 u and 285 u was observed. Knowing the synthetic pathway and fragmentation of the major compound we suggest the following formulae for the impurities: C9H10O2BrN and C15H16O4BN. Further evidence to the first impurity is the detected isotope pattern, corresponding to bromine. The existence of the impurities can be explained and avoided by exploring the synthetic pathways used. High performance liquid chromatography/electrospray mass spectrometry was demonstrated to be an important novel analytical instrument to check the purity of BPA prior to clinical studies in BNCT.

AB - The chemical purity of two synthetic 4‐boronophenylalanine (BPA, C9H12O4BN) batches produced by two different pathways were investigated by high performance liquid chromatography/electrospray mass spectrometry. Currently, BPA is one of the most important clinical boron carriers in boron neutron capture therapy (BNCT). Low energy tandem mass spectrometry was used to elucidate the structure of BPA and two minor signals eluting later than the major compound. In the mass spectrom a very intense singly charged [M+H]+ ion m/z 209 was observed. The ratio of 10B/11B was estimated also. The product‐ion spectrum of BPA shows distinct losses of 18, 46 and 89 u. Based on the fragmentation of the major compound two impurities were characterized. In both cases an intense molecular ion, 244 u and 285 u was observed. Knowing the synthetic pathway and fragmentation of the major compound we suggest the following formulae for the impurities: C9H10O2BrN and C15H16O4BN. Further evidence to the first impurity is the detected isotope pattern, corresponding to bromine. The existence of the impurities can be explained and avoided by exploring the synthetic pathways used. High performance liquid chromatography/electrospray mass spectrometry was demonstrated to be an important novel analytical instrument to check the purity of BPA prior to clinical studies in BNCT.

U2 - 10.1002/(SICI)1097-0231(19980831)12:16<1118::AID-RCM289>3.0.CO;2-1

DO - 10.1002/(SICI)1097-0231(19980831)12:16<1118::AID-RCM289>3.0.CO;2-1

M3 - Article

VL - 12

SP - 1118

EP - 1122

JO - Rapid Communications in Mass Spectrometry

JF - Rapid Communications in Mass Spectrometry

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ER -