PENGEMBANGAN METODE KROMATOGRAFI CAIR KINERJA TINGGI UNTUK PENETAPAN KADAR SIMULTAN EMPAT KOMPONEN OBAT PADA TABLET ANTI TBC 4-FDC

Sholihul Khoiri, Prof. Dr. Sudibyo Martono, M.S., Apt

2014 | Tesis | S2 Ilmu Farmasi

Telah dilakukan penelitian mengenai pengembangan metode kromatograf cair kinerja tinggi (KCKT) untuk penetapan kadar secara simultan empat komponen obat yakni: rifampisin, isoniazid, pirazinamid, dan etambutol hidroklorida, dalam tablet anti tuberculosis (TBC) 4-FDC (fixed dose combination). Untuk meningkatkan sensitivitas serapan UV etambutol hidroklorida, digunakan teknik derivatisasi prakolom dengan agen penderivat phenethyl isocyanate (PEIC). Hasil optimasi metode sebagai berikut: agen penderivat yang digunakan adalah 1:6 terhadap molaritas etambutol hidroklorida, laju alir fase gerak 1,5 mL/menit, suhu kolom oven 30oC dan panjang gelombang 210 nm. Fase gerak yang digunakan adalah sistem gradien antara asetonitril dan larutan 20 mM dapar fosfat pH 6,8 yang mengandung TEA 1,5 mL. Metode divalidasi dengan parameter selektivitas/spesifisitas, linearitas, ketelitian, ketepatan, batas deteksi, batas kuantifikasi, dan uji ketahanan/robustness. Hasil optimasi dan validasi menunjukkan bahwa metode yang dikembangkan dan divalidasi sederhana, cepat, selektif, teliti, akurat dan sesuai untuk penetapan kadar tablet 4-FDC secara rutin.

Researches had be conducted on the development of high-performance liquid chromatography (HPLC) method for the simultaneous quantification of four components: rifampicin, isoniazid, pyrazinamide, and ethambutol hydrochloride (HCl), contain in anti-tuberculosis (TBC) 4-FDC (fixed dose combination) tablet. In increasing the sensitivity of the UV absorption of ethambutol hydrochloride, the pre-column derivatization technique with derivating agent phenethyl isocyanate (PEIC) was used. The results of optimization methods as follows: derivating solution used was 1:6 against molarity ethambutol hydrochloride, mobile phase flow rate of 1.5 mL/minutes, column oven temperature of 30oC and wavelengths of 210 nm. The mobile phase used was a gradient system between acetonitrile and 20 mM phosphate buffer solution of pH 6.8 containing TEA of 1.5 mL. The method was validated with the parameters selectivity/specificity, linearity, accuracy, precision, detection limit, quantification limit, and a test of endurance/robustness. The optimization and validation results showed that this method is simple, rapid, selective/specific, thorough, accurate, and appropriate for the quantification of 4-FDC tablets on a regular basis.

Kata Kunci : KCKT, derivatisasi, rifampisin, isoniazid, pirazinamid, etambutol hidroklorida