Development and validation of analytical method for determination of elemental impurities in erythromycin

Eritromicin je antibiotik u klasi makrolida, strukturno sličnih spojeva koje karakterizira makrociklični prsten. Izoliran je 1952. godine iz Streptomyces erythreus. U ovom radu, razvijena je i validirana brza i učinkovita metoda s kojom se mogu odrediti, u jednom snimanju, sva elementarna onečišćenja propisana ICH Q3D smjernicom u eritromicinu koristeći masenu spektroskopiju s induktivno spregnutom plazmom (ICP-MS). Ispitivanje topljivosti eritromicina pokazalo je da se 100 mg eritromicina izvrsno otapa u 1 mL H2O2 i 1 mL HCl. Kod validacije analitičke metode ispitivani su parametri: linearnost, točnost, granica određivanja, preciznost i ponovljivosti. Rezultati provedenih validacijskih mjerenja za sve parametre nalazili su se unutar unaprijed postavljenih granica pojedinog parametra. Time se pokazalo da je analitička metoda stabilitetno indikativna i prikladna za određivanje onečišćenja u eritromicinu u propisanim uvjetima. Metoda je pokazala da ispitivani uzorak eritromicina ne sadrži elementarna onečišćenja, osim vanadija u koncentraciji manjoj od specifikacije prema ICH te samog limita kvantifikacije, što znači da je uzorak u skladu s propisanim zahtjevima.Erythromycin is an antibiotic belonging to the macrolide class, structurally similar compounds which are characterized by a macrocyclic ring. It was isolated from Streptomyces erythreus in 1952.In this paper an effective method was developed and validated with which it is possible to determine all elementary impurities proposed by ICH Q3D guideline in erythromycin using inductively coupled plasma mass spectrometry (ICP-MS) in a single screening. Solubility testing had shown that 100 mg of erythromycin is excellently soluble in 1 mL of H2O2 i 1 mL of HCL.Following parameters were tested for method validation: linearity, accuracy, limit of quantification, precision and repeatability. Results of the conducted measuring for all parameters were found within boundaries set in advance for each parameter. That has shown that the analytical method is indicative of stability and appropriate for determining impurities in erythromycin within proposed conditions. Method has shown that the tested erythromycin does not contain elementary impurities except for vanadium in a concentration smaller than ICH specification and the limit of quantification meaning that the sample is in accordance with regulatory requirements