title: A new, rapid, stability-indicating UPLC method for separation and determination of impurities in amlodipine besylate, valsartan and hydrochlorothiazide in their combined tablet dosage form.
abstract: A new rapid stability-indicating UPLC method for separation and determination of impurities in amlodipine besylate, valsartan and hydrochlorothiazide in their combined tablet dosage form was developed. The separation of Ph. Eur. related substances of amlodipine besylate (A, B, D, E, F, G), hydrochlorothiazide (A, B, C), valsartan (B, C), two other valsartan impurities (S)-2-(N-{[2'-cyanobiphenyl-4-yl]methyl}pentanamido)-3-methylbutanoic acid and (S)-3-methyl-2-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methylamino}butanoic acid and several unknown impurities was achieved by reversed phase liquid chromatography with UV detection. The detection wavelengths were set as follows: 225nm for valsartan, its impurities and for the impurity D of amlodipine, 271nm for hydrochlorothiazide and its impurities and 360nm for amlodipine and its impurities except for impurity D. Zorbax Eclipse C8 RRHD (100mm×3.0mm, 1.8μm) was used as a separation column and the analytes were eluted within 11min by a programmed gradient mixture of 0.01M phosphate buffer pH 2.5 and acetonitrile. The method was successfully validated in accordance to the International Conference of Harmonization (ICH) guidelines for amlodipine besylate and its impurity D, valsartan and its impurity C and hydrochlorothiazide and its impurities A, B and C. The triple-combined tablets were exposed to thermal, higher humidity, acid, alkaline, oxidative and photolytic stress conditions. Stressed samples were analyzed by the proposed method. All the significant degradation products and impurities were satisfactory separated from each other and from the principal peaks of drug substances. The peak purity test complied for peaks of amlodipine, valsartan and hydrochlorothiazide in all the stressed samples and indicated no co-elution of degradation products. The method was found to be precise, linear, accurate, sensitive, specific, robust and stability-indicating and could be used as a routine purity test method for amlodipine besylate, valsartan, hydrochlorothiazide and their pharmaceutical combinations.
authors.affiliation: Zentiva, k.s., Praha, U Kabelovny 130, 102 37 Praha 10, Czech Republic; Department of Analytical Chemistry, Charles University in Prague, Faculty of Science, Hlavova 8, 128 43 Praha 2, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Vojta
authors.affiliation: Zentiva, k.s., Praha, U Kabelovny 130, 102 37 Praha 10, Czech Republic.
authors.forename: Aleš
authors.initials: A
authors.lastname: Jedlička
authors.affiliation: Department of Analytical Chemistry, Charles University in Prague, Faculty of Science, Hlavova 8, 128 43 Praha 2, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Coufal
authors.affiliation: Zentiva, k.s., Praha, U Kabelovny 130, 102 37 Praha 10, Czech Republic. Electronic address: Lucie.Janeckova@zentiva.cz.
authors.forename: Lucie
authors.initials: L
authors.lastname: Janečková
mesh_terms: D017311:Amlodipine / Q000737:chemistry / Q000302:isolation & purification*; D000959:Antihypertensive Agents / Q000737:chemistry / Q000302:isolation & purification*; D002851:Chromatography, High Pressure Liquid; D004338:Drug Combinations; D004355:Drug Stability; D006852:Hydrochlorothiazide / Q000737:chemistry / Q000302:isolation & purification*; D057230:Limit of Detection; D012015:Reference Standards; D015203:Reproducibility of Results; D012996:Solutions; D013607:Tablets; D000068756:Valsartan / Q000737:chemistry / Q000302:isolation & purification*
chemical_list: D000959:Antihypertensive Agents; D004338:Drug Combinations; D012996:Solutions; D013607:Tablets; D006852:Hydrochlorothiazide; D017311:Amlodipine; D000068756:Valsartan
keywords: Amlodipine; Hydrochlorothiazide; Impurities; UPLC; Valsartan