Analysis Of Pyronaridine And Pyronaridine Tetraphosphate Using High Performance Liquid Chromatography And High Resolution Nuclear Magnetic Resonance Spectroscopy

• Main Author: Saurajen Pillay, Shubhadra Pillay
• Format: Thesis
• Language: English
• Published: 2006
• Subjects: R735-854 Medical education. Medical schools. Research
• Online Access: http://eprints.usm.my/31207/1/SHUNHADRA_PILLAY_A.P_SAURAJEN_PILLAY.pdf; http://eprints.usm.my/31207/

Pironaridina (PND), 2-metoksi-7 -kloro-1 0-[3' ,5'-bis-(pyrrolidinil-1-metil)-4'- hidroksianinilo]benzo[b]-1,5-naftiridina (formula molekul: C29H32CIN502) yang disintesiskan oleh Zheng et al pada awal 1970an telah digunakan sebagai ubat antimalaria selama 20 tahun. la berwarna merah bata, dengan rasa pahit dan tidak berbau dengan takat lebur pada suhu 174-176 °C. Bagi tujuan formulasi ubat, PND diubah kepada terbitan fosfatnya iaitu pironaridina tetrafosfat (PNDT) yang terlarut dalam air (formula molekul: C29H32CIN502.4H3P04) dan mempunyai takat lebur pada 227-230 °C. Kajian yang dilakukan ke atas PNDT sebelum ini hanya menunjukkan satu puncak pad a kromatogram apabila dianalisis dengan menggunakan kromatografi cecair prestasi tinggi (KGPT). Tetapi, dengan menggunakan kaedah terubahsuai Jayaraman yang dikembangkan oleh Karupiah (2003), tiga puncak diperhatikan pada kromatogram. Tiga puncak ini dilabel sebagai komponen B pad a 10.0 min, X pada 21.2 min dan Y pad a 24.3 min. Sebatian B diekstrak dan pencirian struktur sebatian tersebut dilakukan. Akan tetapi, untuk memastikan identiti komponen B, informasi struktur PND dan PNDT perlu ditentukan. Sehingga sekarang, data NMR yang wujud hanya daripada spektrum yang dirakam pada 2.11 Tesla (T) (90 MHz untuk 1H). Pyronaridine (PND), 2-methoxy-7 -chloro-1 0-[3' ,S'-bis-(pyrrolidinyl-1-methyl)-4'hydroxyanilino] benzo[b]-1 ,S-napthyridines (molecular formula: C29H32CINs02), synthesized by Zheng et al. in the early 1970s, has been used in China for over 20 years as an antimalarial drug. It is an odourless, brick red powder with a bitter taste and decomposes at 174-176 °c. For drug formulation purposes, PND is converted to its water-soluble tetraphosphate derivative, PNDT (molecular formula: C29H32CINs02.4H3P04) that has a melting point of 227-230 °c. All previous studies conducted on PND and PNDT using HPLC showed only one peak present in the chromatogram. However, the modified version of Jayaraman's HPLC method developed by Karupiah (2003) showed the presence of three peaks. These were labelled as component B at 10.0 min, X at 21.2 min and Y at 24.3 min. Component B was then extracted and characterized. However, in order to ascertain its identity, detailed structural information of both PND and PNDT must first be established. To date, the only NMR data available in literature on PND was deduced from a proton spectrum recorded at 2.11 Tesla (T) (90 MHz in lH).