コンテンツへスキップ
Merck
  • Stability-indicating RP-LC method for determination of azilsartan medoxomil and chlorthalidone in pharmaceutical dosage forms: application to degradation kinetics.

Stability-indicating RP-LC method for determination of azilsartan medoxomil and chlorthalidone in pharmaceutical dosage forms: application to degradation kinetics.

Analytical and bioanalytical chemistry (2014-09-06)
Walid M Ebeid, Ehab F Elkady, Asmaa A El-Zaher, Ramzia I El-Bagary, Gabor Patonay
要旨

A RP-LC method was developed and validated for simultaneous determination of the active components, azilsartan medoxomil (AZL) and chlorthalidone (CLT), in their novel antihypertensive combined recipe. The chromatographic separation was achieved on an Eclipse XDB-C18 (4.6 × 150 mm, 5 μm) column using a mobile phase consisting of methanol/potassium hydrogen phosphate buffer (pH 8, 0.05 M) (40:60, v/v) in isocratic mode. The flow rate was maintained at 0.8 mL min(-1) at ambient temperature. Detection was carried out at 210 nm. The method was validated according to the ICH guidelines. Linearity, accuracy, and precision were satisfactory over the concentration range of 5.0-50.0 and 2.5-25.0 μg mL(-1) for AZL and CLT, respectively (r (2) = 0.9999). LODs for AZL and CLT were 0.90 and 0.32 μg mL(-1), whereas LOQs were 2.72 and 0.98 μg mL(-1), respectively. Both drugs were subjected to forced degradation studies under hydrolysis (neutral, acidic, and alkaline), oxidative, and photolytic extensive stress conditions. The proposed method is stability indicating by the resolution of the investigated drugs from their degradation products. Moreover, the kinetics of the acidic degradation of AZL as well as the kinetics of the alkaline degradation of CLT were investigated. Arrhenius plots were constructed and the apparent first-order rate constants, half-life times, shelf-life times, and the activation energies of the degradation processes were calculated. The method was successfully applied for the determination of the studied drugs simultaneously in their coformulated tablet. The developed method is specific and stability indicating for the quality control and routine analysis of the cited medications in their pharmaceutical preparations.

材料
製品番号
ブランド
製品内容

Sigma-Aldrich
酢酸アンモニウム, ACS reagent, ≥97%
Sigma-Aldrich
酢酸アンモニウム, ≥99.99% trace metals basis
Sigma-Aldrich
酢酸アンモニウム, for molecular biology, ≥98%
Sigma-Aldrich
酢酸アンモニウム 溶液, for molecular biology, 7.5 M
Sigma-Aldrich
過酸化水素 溶液, contains ~200 ppm acetanilide as stabilizer, 3 wt. % in H2O
Sigma-Aldrich
過酸化水素 溶液, purum p.a., ≥35% (RT)
Sigma-Aldrich
酢酸アンモニウム, 99.999% trace metals basis
Sigma-Aldrich
酢酸アンモニウム, JIS special grade, ≥97.0%
Sigma-Aldrich
過酸化水素 溶液, JIS special grade, 30.0-35.5%
Millipore
過酸化水素 溶液, 3%, suitable for microbiology
Sigma-Aldrich
過酸化水素 溶液, SAJ first grade, ≥30.0%
Supelco
酢酸アンモニウム, LiChropur, eluent additive for LC-MS
Sigma-Aldrich
酢酸アンモニウム, reagent grade, ≥98%
Sigma-Aldrich
Ser-Phe-Leu-Leu-Arg-Asn-Pro-Asn-Asp-Lys-Tyr-Glu-Pro-Phe, ≥97% (HPLC)
Sigma-Aldrich
酢酸アンモニウム, BioXtra, ≥98%
Sigma-Aldrich
酢酸アンモニウム 溶液, BioUltra, for molecular biology, ~5 M in H2O
Sigma-Aldrich
酢酸アンモニウム, BioUltra, for molecular biology, ≥99.0%
Sigma-Aldrich
酢酸アンモニウム 溶液, 50 % (w/v), suitable for iron determination
Sigma-Aldrich
酢酸アンモニウム, SAJ first grade, ≥97.0%
Sigma-Aldrich
酢酸アンモニウム 溶液, 50 % (w/v)