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Titolo:
Purification and identification of an impurity in bulk hydrochlorothiazide
Autore:
Fang, XG; Bibart, RT; Mayr, S; Yin, W; Harmon, PA; McCafferty, JF; Tyrrell, RJ; Reed, RA;
Indirizzi:
Merck & Co Inc, Regulatory & Analyt Sci, W Point, PA 19486 USA Merck & Co Inc W Point PA USA 19486 y & Analyt Sci, W Point, PA 19486 USA Merck & Co Inc, Pharmaceut Anal & Control, W Point, PA 19486 USA Merck & Co Inc W Point PA USA 19486 Anal & Control, W Point, PA 19486 USA Merck & Co Inc, N Amer Stabil Unit, W Point, PA 19486 USA Merck & Co Inc W Point PA USA 19486 er Stabil Unit, W Point, PA 19486 USA Merck & Co Inc, Qual Serv Amer, W Point, PA 19486 USA Merck & Co Inc W Point PA USA 19486 Qual Serv Amer, W Point, PA 19486 USA
Titolo Testata:
JOURNAL OF PHARMACEUTICAL SCIENCES
fascicolo: 11, volume: 90, anno: 2001,
pagine: 1800 - 1809
SICI:
0022-3549(200111)90:11<1800:PAIOAI>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Keywords:
hydrochlorothiazide; HCTZ; DSA; impurity; diuretic;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
9
Recensione:
Indirizzi per estratti:
Indirizzo: Fang, XG Merck & Co Inc, Regulatory & Analyt Sci, WP38-3, W Point, PA 19486 USA Merck & Co Inc WP38-3 W Point PA USA 19486 W Point, PA 19486 USA
Citazione:
X.G. Fang et al., "Purification and identification of an impurity in bulk hydrochlorothiazide", J PHARM SCI, 90(11), 2001, pp. 1800-1809

Abstract

Hydrochlorothiazide (6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7sulfonamide 1,1-dioxide) (HCTZ) 1 is a widely used diuretic and anti-hypertensive. Recently, the Pharmeuropa recognized a new impurity initially thought tobe an HCTZ dimes 6, which consists of the active drug (HCTZ) linked via the former beta -ring methylene to a known degradate, 5-chloro-2,4-disulfamylaniline 2. In an effort to meet a new requirement, an analytical high-pressure liquid chromatography method was developed that was selective and sensitive to the subject impurity. The impurity was concentrated and purified using a combination of solid phase extraction and reverse-phase high-pressureliquid chromatography. Subsequently, the impurity has been identified as aspecific HCTZ-CH2-HCTZ isomer utilizing a variety of analytical techniques, including hydrolysis, ultraviolet spectroscopy, liquid chromatography/mass spectrometry, and H-1 and C-13 nuclear magnetic resonance (NMR) spectroscopy. The data resulting from the application of these analytical techniquesconfirm the identity of the impurity as a methylene bridged pair of HCTZ molecules; however, a total of six possible isomers 7a-f exist because of the presence of three reactive amines/sulfonamides on each HCTZ molecule. Oneunique molecular structure (4-[{6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide-1,1-dioxide}-methyl]-chloro-3-hydro-H-1,2,4-benzothiadiazine-7-sulfonamide-1,1-dioxide) 7f was identified using two-dimensional COSY, NOESY, and TOCSY H-1 NMR experiments. (C) 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/03/20 alle ore 19:54:25