İsmail Tuncer DEĞİM, Ahmet AYDIN, Yalçın ÖZKAN, Hüsamettin GÜL, Ahmet SAYAL, Cemal AKAY

Rapid and simultaneous determination of acetylsalicylic acid, paracetamol, and their degradation and toxic impurity products by HPLC in pharmaceutical dosage forms

Amaç: Ticari farmasötik şekiller içinde bulunan ilaç moleküllerininin ve saflıklarının saptanması, toksikolojik ve farmakolojik bakımdan önemlidir. Farmasötik şekillerin hazırlanması sırasında saflık ve ilgili bozulma ürünlerinin izlenebilmesi için ileri metotlara ihtiyaç vardır. Bu çalışmanın amacı farmasötik dozaj şekillerinde parasetamol, asetil salisilik asit (ASA) ve bunların yıkılma/katışıklık ürünlerinin HPLC yöntemi ile hızlı ve eşzamanlı olarak saptanmasıdır. Yöntemler: Ticari dozaj şekillerindeki parasetamol, ASA, askorbik asit ve bu preparatlarda yıkılma ya da katışıklık ürünü olarak bulunan salisilik asit ve p-kloroasetanilitin saptanması için bir reverse faz HPLC (yüksek performanslı sıvı kromatografisi) metodu geliştirilmiştir. Bu bileşikler C18 ters faz kolon kullanılarak mobil fazı metanol:su (35:65;v/v) karışımından oluşan pH'sı % 10'luk ortofosforik asitle 3.1'e ayarlanan akış hızı 1.8 ml/dakika ve 235 nm' de izlenmiştir. Sülfametaksazol internal standart olarak kullanılmıştır. Bulgular: Yeni geliştirilen HPLC metodu, parasetamol, asetilsalisilik asid, askorbik asid, salisilik asid ve pkloroasetanilit için sırasıyla 0.5-4.0, 0.75-6.0, 0.75-6.0, 1.0-12.0 ve 1.0-12.0 mg/ml aralıklarında doğrusal bulunmuştur. Tekrarlanabilirlik ve geri kazanım için göreceli standart sapma % 2'nin altında olarak saptanmıştır. Sonuç: Bu çalışmada geliştirilen RP-HPLC metodu, parasetamol, ASA, askorbik asit içeren farmasötik dozaj şekillerinde ilaç molekülleri ve bunların bozulma ve/veya katışıklık (safsızlık) ürünleri için hızlı, basit ve herhangi bir ön ekstraksiyon gerektirmeyen ve başarıyla uygulanabilecek bir yöntemdir.

Bazı farmasötik dozaj şekillerinde bulunan asetil salisilik asit, parasetamol ve bunların yıkılma/katışıklık ürünlerinin hızlı ve eşzamanlı bir HPLC yöntemi ile saptanması

Aims: Determinations of drug impurity and drug degradation products are very important from both pharmacological and toxicological perspectives. Establishment of monitoring methods for impurities and degradation products during pharmaceutical development is necessary because of their potential toxicity. The aim of this study was to develop a rapid and simultaneous determination method for paracetamol and acetylsalicylic acid (ACA) and their degradation and toxic impurity products by high performance liquid chromatography (HPLC) in pharmaceutical dosage forms. Materials and Methods: A reverse phase (RP)-HPLC method for the simultaneous analysis of paracetamol, ACA, and ascorbic acid and their degradation and impurity products such as salicylic acid (SA) and pchloroacetanilide was developed and applied to the determination of these compounds in commercial dosage forms. These compounds were well separated on a Bondapak C18 reverse phase column using a mobile phase consisting of a mixture of methanol: water (35:65; v/v) adjusted to pH 3.1 with 10% orthophosphoric acid at a flow rate of 1.8 ml.min"1 and the effluent was monitored at 235 nm. Sulfamethoxazole was used as an internal standard. Results: The proposed method was linear in the ranges of 0.5-4.0, 0.75-6.0, 0.75-6.0, 1.0-12.0 and 1.0- 12.0 ug ml"1 for paracetamol, ACA, ascorbic acid, SA and p-chloroacetanilide, respectively. Relative standard deviations for repeatability, reproducibility and recovery were below 2%. Conclusions: In this study, a RP-HPLC method, which is simple, rapid and does not require any separation step for each drug, was successfully applied for the quantitative assay of paracetamol, ACA, ascorbic acid, and their degradation and toxic impurity products in commercial tablet dosage forms.

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