Çağrı ÖZKURT, Alper ÜNAL, Orhan KILIÇ, Deniz ÇIKLA YILMAZ

Tablet Formülasyonundaki Nateglinid’in Pentaflorofenil Core-Shell (Çekirdek-Kabuk) Kolon Kullanılarak HPLC ile Tayini

Nateglinid Tip 2 Diabetes mellitus tedavisinde kullanılan bir insülin salgılatıcıdır. Bu çalışmada tablet formülasyonundaki nateglinidin tayini için basit bir analitik yöntem geliştirilmiştir. İzokratik ve ters faz yüksek performanslı sıvı kromatografi (HPLC) yöntemi, sabit faz olarak Kinetex pentaflorofenil (PFP) (5μm partikül boyutu ve 4.6 x 150 mm kolon boyutu) core-shell kolon, hareketli faz olarak 0.05 M Na2HPO4 (pH=2.0) / metanol (30:70 v/v) karışımı 1.0 mL dk-1 akış ve 215 nm’de diod dizi dedektör kullanılarak geliştirilmiştir. Termostat kontrollü kolon sıcaklığı 22°C’dir. Bu koşullar altında nateglinid 4.779 dakika alıkonma zamanı ve simetrik bir pik şekliyle elüe olmuştur. Kuyruklanma faktörü, kapasite faktörü ve teorik plaka sayısı gibi sistem uygunluk parametreleri hesaplanmıştır. Analitik yöntem validasyonunun gerektirdiği testler Uluslararası Uyum Konseyi (ICH) yönergelerine göre yapılmıştır. y= 10.818x + 4.7048 (R2= 0.998) doğru denklemi ile 2.54 – 40.70μg mL-1 konsantrasyon aralığında doğrusallık bulundu. Teşhis sınırı 1.07 ve tayin sınırı 2.54 μg mL-1’dir. Yöntemin doğruluğu geri kazanım çalışması ile belirlendi ve yüzde geri kazanım 98.78 – 100.76 aralığında hesaplandı. Gün içi ve günler arası tekrarlanabilirlik çalışmalarıyla elde edilen pik alanlarının bağıl standart sapma değerleri ICH limitleri iç

Anahtar Kelimeler:

validasyon, HPLC, nateglinid, pentaflorofenil, core-shell kolon

Determination of Nateglinide in Tablet Formulation by HPLC Using a Pentafluorophenyl Core-Shell Column

Nateglinide is an insulin secretagogue which has been used for the treatment of Type 2 Diabetes mellitus. A simple analytical methodology for determination of nateglinide in tablet formulation is described. An isocratic reversed phase high performance liquid chromatographic (HPLC) method was developed using Kinetex pentafluorophenyl (PFP) (5μm particle size and 4.6 x 150 mm id) core-shell column as stationary phase and 0.05 M Na2HPO4 (pH=2.0) / methanol (30:70 v/v) mixture as mobile phase with the flow rate of 1.0 mL min-1 and diode-array detector at 215 nm. Column was termostated at 22°C. Under these conditions nateglinide was eluted with a symmetrical peak shape and the retention time was 4.779 minutes. The system suitability parameters such as tailing factor, capacity factor and theoretical plate were evaluted. The method was validated as per International Council on Harmonisation (ICH) guidelines. Linearity was obtained in the 2.54 - 40.70 μg mL-1 concentration range with equation y= 10.818x + 4.7048 (R2= 0.998). Limit of detection and limit of quantification were 1.07 and 2.54 μg mL-1. Accuracy of the method was tested by recovery studies which were in the range of 98.78 - 100.76 %. The intra-day and inter-day precision studies were carried out and the relative standard deviation values of peak areas were within ICH limits. The proposed method was successfully applied to the determination of nateglinide in tablet dosage form.

Keywords:

Validation, HPLC, Nateglinide, pentafluorophenyl, core shell column,

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