Development and validation of a capillary electrophoresis method for the determination of sulfate in indinavir sulfate raw material

Abstract

O presente trabalho descreve um método simples e rápido por eletroforese capilar, utilizando detecção indireta (230 nm) para determinação quantitativa de sulfato em sulfato de indinavir (matéria-prima). Uma solução contendo 10 mmol L -1 de molibdato de amônio e 0,15 mmol L -1 de brometo de cetiltrimetilamônio (pH 7,5) foi utilizada como eletrólito de corrida. As amostras foram injetadas hidrodinamicamente com pressão 5000 Pa durante 3 s. A resposta foi linear no intervalo entre 10,1 μg mL -1 a 79,8 μg mL -1 . Os limites de detecção e quantificação foram de 0,34 e 1,13 μg mL -1 , respectivamente. A precisão intra-dia, determinada como desvio padrão relativo, foi de 2,8% para dez preparações independentes da amostra. Os valores de recuperação para três diferentes níveis de concentração variaram de 96,9 a 102,4%. A metodologia foi aplicada a amostras reais. A concentração de sulfato na amostra variou de 13,3 a 13,5% (m/m, calculado com relação ao material seco).In this work, a simple and fast capillary electrophoresis method using indirect UV detection (230 nm) for the quantitative determination of sulfate in the indinavir sulfate raw material was described. A running electrolyte consisting of 10 mmol L -1 ammonium molybdate containing 0.15 mmol L -1 cetyltrimethylammonium bromide (pH 7.5) was used. Samples were injected hydrodynamically by applying 5000 Pa pressure during 3 s. The response was linear from 10.1 μg mL -1 to 79.8 μg mL -1 . Limits of detection and quantification were 0.34 and 1.13 μg mL -1 , respectively. The intra-day precision expressed as relative standard deviation was 2.8% for 10 independent sample preparations. Recoveries varying from 96.9 to 102.4% at three concentration levels were obtained. The methodology was successfully applied for real samples. The concentration of sulfate in indinavir sulfate raw material varied from 13.3 to 13.5% (m/m calculated as anhydrous base).Keywords: indinavir sulfate, capillary electrophoresis, sulfate, validation, HIV IntroductionIndinavir sulfate was approved by the FDA (Food and Drugs Administration) on March 13, 1996, for use in combination with other protease inhibitors, nucleoside analogues or reverse transcriptase inhibitors for the treatment against acquired immune deficiency syndrome (AIDS).1 Indinavir is prescribed as a sulfate salt due to superior gastrointestinal solubility and absorption when compared with the free base. When drugs are manufactured as salts, an analytical technique is required to confirm that correct levels of counter ion are present. 3 The counter ions of drugs with ionic groups are of importance because the physicochemical properties, stability and bioavailability of the drugs depend on their salt forms. An analytical technique such as ion chromatography (IC) and titrimetry is often used for the analysis of counter ion in pharmaceutical drug substances.3 However, these methods are laborious and time consuming, besides the high maintenance cost of IC technique.Capillary electrophoresis (CE) has been successfully applied to the ana...

Chemical and morphological changes on platinum microelectrode surfaces in AC and DC fields with biological buffer solutions

“…AC and DC electric fields of intensities exceeding 6 V pp /175 mm and AE3 V/ 175 mm are used in microdevices performing electrokinetic separation methods. [22][23][24][25][26][27][28] More drastic changes to microelectrodes were observed in 6 V pp fields as opposed to 1 V pp fields. Oxidation and dissolution of platinum, as well as the possible redeposition of platinum was observed in all cases.…”

Quality Control of Protease Inhibitors

“…Lead nitrate was used instead of lead perchlorate as a titrant employing potentiometric determination using a lead‐specific electrode. Pereira et al15 developed and validated a CE method for the determination of the sulfate ion in IDV drug substance. Another CE method described by Prado et al5 allows the separation of IDV from its degradation impurities in capsules.…”