İzoproterenol hidroklorür içinde izopropilamin hidroklorür tayini, analitik metot geliştirilmesi ve validasyonu
Küçük Resim Yok
Tarih
2023
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Tekirdağ Namık Kemal Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
İzoproterenol hidroklorür; kan damarlarını genişleten, ?1 ve ?2 reseptörleri uyaran sentetik bir katekolamindir. İzopropilamin, izoproterenol hidroklorür ilaç etken maddesinin sentezinde kullanılan başlangıç maddelerinden biri olup, son üründe miktarı Uluslararası İlaç Uyum Konseyi (ICH)'ne göre %0.15'i geçmemesi gerektiğinden, kantifikasyonu analitik metot ile kontrol edilir. Bu çalışmada izopropilamin safsızlığı yüksek performanslı sıvı kromatografisi (HPLC-UV) sistemi kullanılarak ve kolon öncesi türevlendirme yapılarak tayin edilmiştir. Yöntemde türevlendirme ajanı olarak 1-naftil izotiyosiyanat kullanılmış, oluşan 1-izopropil-3-(naftalen-1-il)tiyoüre molekülü 230 nm dalga boyunda izlenmiştir. Numunedeki analitik ayrım Phenomenex Luna Phenyl-Hexyl kolon (4,6 mm x 250 mm; 5.0 µm), %0.1 o-fosforik asit ve 70:20:10 oranında asetonitril, methanol ve su karıştırılmış mobil faz sistemi kullanılarak sağlanmıştır. Metot validasyonu çalışmaları ICH Q2(R1) kılavuzuna göre yapılmıştır. Validasyon parametrelerinden seçicilikte; türevlendirilmiş izopropilamin molekülünün oluşturduğu pikin izoproterenol hidroklorür maddesinin pikinden ve diğer safsızlıkların piklerinden ayrıldığı ve spektral olarak saf olduğu gözlemlenmiştir. Türevlendirilmiş izopropilamin molekülünün stabilitesinin 10 saat olduğu bulunmuştur. Gözlenebilme sınırı (LOD) 0.0021 µg/mL ve alt tayin sınırı (LOQ) 0.0071 µg/mL olarak hesaplanmıştır. Yöntemin hızlı, sağlam, seçici, tekrar edilebilir ve düşük derişimlerde de izopropilamin tayinine olanak sağlayan bir çalışma olduğu görülmüştür. Anahtar Kelimeler: İzoproterenol hidroklorür, İzopropilamin, HPLC, Türevlendirme
Isoproterenol hydrochloride; is a synthetic catecholamine that dilates blood vessels and stimulates ?1 and ?2 receptors. Isopropylamine is one of the starting materials used in the synthesis of isoproterenol hydrochloride active pharmaceutical ingredient, and its quantification is controlled by analytical method, since its amount in the final product should not exceed 0.15% according to the The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). In this study, determination of isopropylamine impurity was performed by high performance liquid chromatography system and pre-column derivatization. In the method, 1-naphthyl isothiocyanate was used as the derivatizing agent and the resulting 1-isopropyl-3-(naphthalen-1-yl)thiourea molecule was monitored at a wavelength of 230 nm. Analytical separation in the sample was made using a Phenomenex Luna Phenyl-Hexyl column (4.6 mm x 250 mm; 5.0 µm), 0.1% o-phosphoric acid and a 70:20:10 ratio acetonitrile, methanol and water mixed mobile phase system. Method validation studies were performed according to the ICH Q2(R1) guideline. Specificity from validation parameters; it was observed that the peak formed by the derivatized isopropylamine molecule was separated from the peak of the isoproterenol hydrochloride substance and the peaks of other impurities and was spectrally pure. The stability of the derivatized isopropylamine molecule was determined as 10 hours. The limit of detection (LOD) was calculated as 0.0021 µg/mL and the limit of quantification (LOQ) as 0.0071 µg/mL. It has been observed that the method is fast, robust, selective, reproducible and allows the determination of isopropylamine at low concentrations. Keywords: Isoproterenol hydrochloride, Isopropilamine, HPLC, Derivatization
Isoproterenol hydrochloride; is a synthetic catecholamine that dilates blood vessels and stimulates ?1 and ?2 receptors. Isopropylamine is one of the starting materials used in the synthesis of isoproterenol hydrochloride active pharmaceutical ingredient, and its quantification is controlled by analytical method, since its amount in the final product should not exceed 0.15% according to the The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). In this study, determination of isopropylamine impurity was performed by high performance liquid chromatography system and pre-column derivatization. In the method, 1-naphthyl isothiocyanate was used as the derivatizing agent and the resulting 1-isopropyl-3-(naphthalen-1-yl)thiourea molecule was monitored at a wavelength of 230 nm. Analytical separation in the sample was made using a Phenomenex Luna Phenyl-Hexyl column (4.6 mm x 250 mm; 5.0 µm), 0.1% o-phosphoric acid and a 70:20:10 ratio acetonitrile, methanol and water mixed mobile phase system. Method validation studies were performed according to the ICH Q2(R1) guideline. Specificity from validation parameters; it was observed that the peak formed by the derivatized isopropylamine molecule was separated from the peak of the isoproterenol hydrochloride substance and the peaks of other impurities and was spectrally pure. The stability of the derivatized isopropylamine molecule was determined as 10 hours. The limit of detection (LOD) was calculated as 0.0021 µg/mL and the limit of quantification (LOQ) as 0.0071 µg/mL. It has been observed that the method is fast, robust, selective, reproducible and allows the determination of isopropylamine at low concentrations. Keywords: Isoproterenol hydrochloride, Isopropilamine, HPLC, Derivatization
Açıklama
Fen Bilimleri Enstitüsü, Kimya Ana Bilim Dalı
Anahtar Kelimeler
Kimya, Chemistry
