ICP-MS Analysis and Validation by Microwave Digestion System for Determination of Heavy Metals in Allergy and Cancer Drugs Taken Orally

Yıl 2023, Cilt: 11 Sayı: 4, 1700 - 1714, 24.10.2023

Elif Köse Aslıhan Dalmaz Sezen Sivrikaya Özak

https://doi.org/10.29130/dubited.1196985

Öz

The drug, one of the most important products that cannot be replaced in the field of health, prevents all threats to human health when used in place and dosage. Therefore, it has an important place in public health. Determination of the amounts and impurities of various elements used in drug production is an important parameter. According to the ICH Q3D(R1) international compliance conference guide, methods by which limit concentrations can be determined for elemental impurities by applying inductively coupled plasma (ICP) analysis to drugs are specified. In this study, the sample preparation step in the analysis of 23 elements in cancer and allergy drugs in tablet form was optimized by microwave digestion, and method development and validation studies were carried out for these drugs with inductively coupled plasma-mass spectrometry (ICP-MS). When the analysis results were evaluated, it was seen that the data obtained were by the limit values specified in the ICH. Detection and quantification limits of the developed method, and relative standard deviation values were determined, and recovery studies were carried out by adding standards at 4 different concentrations to determine the method's precision. The correlation coefficients obtained for heavy metals in this study ranged from 0.9993 to 1.000, while the detection limit was found to be between 0.001 and 1.756 µg/L. Thus, the reliability and precision of the validation study developed has been determined and it has been shown that this method can be used in similar drug samples.

Anahtar Kelimeler

Validation, Heavy metal, Microwave digestion, Inductively coupled plasma-mass spectrometry, Drug

Destekleyen Kurum

Düzce University Scientific Project

Proje Numarası

2022.05.03.1325

Teşekkür

We thank to Nobel Drug Pharmaceutical R&D Center (Nobel-Ilac Ar-Ge Merkezi) for their support of this study

Oral Yol ile Alınan Alerji ve Kanser İlaçlarında Ağır Metallerin Tayini için Mikrodalga Çözünürleştirme Sistemi ile ICP-MS Analizi ve Validasyonu

Öz

Sağlık alanında yeri doldurulamayacak ürünlerin en önemlilerinden biri olan ilaç yerinde ve dozunda kullanıldığında insan sağlığı için oluşan tüm tehdit unsurlarına engel olmaktadır. Toplum sağlığı açısından değerlendirildiğinde önemi oldukça büyüktür. İlaç üretiminde kullanılan çeşitli elementlerin miktarlarının ve safsızlıklarının belirlenmesi çok önemli bir parametredir. İlaçlar için indüktif eşleşmiş plazma (ICP) analizi, Uluslararası uyum konferansı kılavuzu ICH Q3D(R1) referans alınarak elementel safsızlıkların eşik konsantrasyonlarının belirlenmesinde kullanılan bir yöntemdir. Bu çalışmada tablet formundaki kanser ve alerji ilaçlarındaki 23 elementin analizinde örnek hazırlama basamağı mikrodalga çözünürleştirme işlemi ile optimize edilmiş ve indüktif eşleşmiş plazma-kütle spektrometresi (ICP-MS) ile bu ilaçlar için metot geliştirme ve validasyon çalışmaları gerçekleştirilmiştir. Yapılan analiz sonuçları değerlendirildiğinde elde edilen verilerin ICH’de belirtilen sınır değerlere uygun olduğu görülmüştür. Geliştirilen yöntemin belirleme ve tayin limitleri, rölatif standart sapma değerleri belirlenmiş ve ayrıca yöntemin kesinliğini tespit etmek amacıyla test örneklerine 4 farklı konsantrasyonda standart eklemesi yapılarak geri kazanım çalışmaları yapılmıştır. Bu çalışmada ağır metaller için elde edilen korelasyon katsayıları 0,9993 ile 1,000 arasında değişirken dedeksiyon limitleri ise 0,001 ile 1,756 µg/L arasında bulunmuştur. Böylelikle geliştirilen validasyon çalışmasının güvenilirliği ve kesinliği belirlenmiş olup, benzer ilaç örneklerinde bu yöntemin kullanılabilir olduğu gösterilmiştir.

Anahtar Kelimeler

Validasyon, Elementel safsızlık, Mikrodalga çözünürleştirme, İndüktif eşleşmiş plasma-kütle spektrometrisi, İlaç

Proje Numarası

2022.05.03.1325

Kaynakça

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