Journals / Turkish Journal of Medical Sciences / 2008 / Cilt: 38 - Sayı: 2
Rapid and Simultaneous Determination of Acetylsalicylic Acid, Paracetamol, and Their Degradation and Toxic Impurity Products by HPLC in Pharmaceutical Dosage Forms
- Pages
- 167–173
- DOI
- —
Abstract
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 p-chloroacetanilide 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 µg m1-1 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.
Özet
Amaç: Ticari farmasötik flekiller içinde bulunan ilaç moleküllerininin ve safl›klar›n›n saptanmas›, toksikolojik vefarmakolojik bak›mdan önemlidir. Farmasötik flekillerin haz›rlanmas› s›ras›nda safl›k ve ilgili bozulmaürünlerinin izlenebilmesi için ileri metotlara ihtiyaç vard›r. Bu çal›flman›n amac› farmasötik dozaj flekillerindeparasetamol, asetil salisilik asit (ASA) ve bunlar›n y›k›lma/kat›fl›kl›k ürünlerinin HPLC yöntemi ile h›zl› ve eflzamanl› olarak saptanmas›d›r.Yöntemler: Ticari dozaj flekillerindeki parasetamol, ASA, askorbik asit ve bu preparatlarda y›k›lma ya dakat›fl›kl›k ürünü olarak bulunan salisilik asit ve p-kloroasetanilitin saptanmas› için bir reverse faz HPLC (yüksekperformansl› s›v› kromatografisi) metodu gelifltirilmifltir. Bu bileflikler C18 ters faz kolon kullan›larak mobil faz›metanol:su (35:65;v/v) kar›fl›m›ndan oluflan pH’s› % 10’luk ortofosforik asitle 3.1’e ayarlanan ak›fl h›z› 1.8ml/dakika ve 235 nm’ de izlenmifltir. Sülfametaksazol internal standart olarak kullan›lm›flt›r.Bulgular: Yeni gelifltirilen HPLC metodu, parasetamol, asetilsalisilik asid, askorbik asid, salisilik asid ve pkloroasetanilit için s›ras›yla 0.5-4.0, 0.75-6.0, 0.75-6.0, 1.0-12.0 ve 1.0-12.0 mg/ml aral›klar›nda do¤rusalbulunmufltur. Tekrarlanabilirlik ve geri kazan›m için göreceli standart sapma % 2’nin alt›nda olaraksaptanm›flt›r.Sonuç: Bu çal›flmada gelifltirilen RP-HPLC metodu, parasetamol, ASA, askorbik asit içeren farmasötik dozajflekillerinde ilaç molekülleri ve bunlar›n bozulma ve/veya kat›fl›kl›k (safs›zl›k) ürünleri için h›zl›, basit ve herhangibir ön ekstraksiyon gerektirmeyen ve baflar›yla uygulanabilecek bir yöntemdir