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ID 114222
Title Alternative
Determination of Acid Dissociation Constants of Hydrochlorothiazide and Its Degradant through Measurement of the Effective Electrophoretic Mobilities in CZE
Author
Isoda, Masashi Tokushima University
Itoh, Daichi Tokushima University
Keywords
hydrochlorothiazide
degradant
chlorothiazide
capillary zone electrophoresis
acid dissociation constant
Content Type
Journal Article
Description
チアジド系利尿剤の一つであるヒドロクロロチアジドは水中で加水分解により徐々に4-アミノ-6-クロロ-m-ベンゼンジスルホンアミドを生成する.酸解離定数(pKa)などの物理化学定数の決定において分解生成物等の存在は好ましくないが,キャピラリーゾーン電気泳動法では分解生成物を分離することで分解物を含む共存物質の問題を回避して解析することが可能である.本研究では,泳動緩衝液のpHに伴う電気泳動移動度の変化から分解条件下でヒドロクロロチアジドのpKaを決定したところ,分解生成物の共存下で二段階のpKa1=8.95±0.04,pKa2=10.66±0.07が得られた.また,分解生成物である4-アミノ-6-クロロ-m-ベンゼンジスルホンアミドについても電気泳動移動度の変化から二段階のpKaを決定することができ,pKa1=9.27±0.06,pKa2=10.79±0.10が得られた.
Description Alternative
Hydrochlorothiazide, one of the popular diuretics, is degradable in an aqueous solution by hydrolysis, gradually forming 4-amino-6-chloro-m-benzenedisulfonamide. Upon determining the physicochemical constants such as acid dissociation constant (pKa), the coexistence of any degraded species is not desirable. However, equilibrium analysis with the effective electrophoretic mobility measured by capillary zone electrophoresis (CZE) can allow the coexistence of such degraded substances. In this study, acid dissociation constants were determined by CZE with hydrochlorothiazide (HCT) under its degraded conditions. Two steps of the successive acid-dissociation constants have been determined with HCT as pKa1 = 8.95±0.04 and pKa2 = 10.66±0.07; the values agree well with those determined with a freshly prepared HCT solution. Further, two steps of the successive acid-dissociation constants were also determined with the degradant from HCT, 4-amino-6-chloro-m-benzenedisulfonamide, by the CZE analysis utilizing the resolution of the degradant from HCT; pKa1 = 9.27±0.06 and pKa2 = 10.79±0.10 were determined. The potential of the equilibrium analysis by CZE was demonstrated with the degradable HCT.
Journal Title
BUNSEKI KAGAKU
ISSN
05251931
NCID
AN00222633
Publisher
日本分析化学会
Volume
66
Issue
7
Start Page
509
End Page
514
Published Date
2017-07-05
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
jpn
TextVersion
Publisher
departments
Science and Technology