Subakut Sklerozan Panensefalitli Hastaların Plazmasında Aprepitant Tayini İçin Hassas ve Hızlı Bir LC-MS Yönteminin Geliştirilmesi

Year 2025, Volume: 25 Issue: 6, 1301 - 1307

Filiz Arıöz , Gizem Kunal Şalli , Songul Tezcan , Emine Arman Kandırmaz , Mesut Sancar , Bahadır Konuşkan , İbrahim Halil Öncel , Banu Anlar

Abstract

Bu çalışmada, Subakut Sklerozan Panensefalit (SSPE) hastalarının kanındaki aprepitant düzeylerinin rutin olarak izlenmesi için hassas, seçici, hızlı ve doğrulanmış bir Sıvı Kromatografisi-Kütle Spektrometrisi (LC-MS) yöntemi geliştirilmiştir. Geliştirilen bu yöntem, SSPE hastalarında ilaca bağlı potansiyel toksisitenin tespit edilmesi ve izlenmesinde etkili bir şekilde kullanılmıştır. Aprepitant, insan plazmasından sıvı-sıvı ekstraksiyonu yöntemi kullanılarak ekstrakta edilmiştir. Kromatografik analiz için en uygun koşullar, C18 (50 mm x 2,1 mm x 3 µm) kolonu, asetonitril/su (50/50 (%0,2 formik asit) v/v) izokrotik mobil fazı ve 0,40 mL/dakika akış hızı olarak bulunmuştur. Kütle spektrometresinde, pozitif modda, elektrosprey iyonizasyon tekniği ile çalışılmış ve aprepitant 535.20 m/z değerinde tespit edilmiştir. Aprepitant için alıkonma zamanı 2,70 dakika, toplam analiz süresi 4,8 dakika, doğrusal konsantrasyon aralığı 0,0125-3,00 µg/mL (r=0,9976), LOD ve LOQ değerleri sırasıyla 0,01 μg/mL ve 0,03 μg/mL olarak bulunmuştur. Geliştirilen yöntem, SSPE hastalarından alınan plazma örneklerinde aprepitantın konsantrasyonunun tespiti için başarıyla kullanılmıştır. Geliştirilen ve valide edilen bu yöntem seçici, duyarlı ve hızlı bir yöntemdir. Preklinik ve klinik çalışmalarda, aprepitant tespiti için güvenle ve rutin olarak kullanılabilir.

Keywords

Aprepitant , miktar tayini , LC-MS , Subakut sklerozan panensefalit , İnsan plazması

Project Number

This study was funded by Scientific and Technological Research Council of Turkey (TUBITAK), 114S193.

Development of A Rapid and Sensitive LC-MS Method for Determination of Aprepitant Levels in the Plasma of Subacute Sclerosing Panencephalitis Patients

Abstract

In this study, a sensitive, selective, rapid, and validated Liquid Chromatography-Mass Spectrometry (LC-MS) method has been developed for routine monitoring of aprepitant concentrations in the blood of patients with subacute sclerosing panencephalitis (SSPE). The developed method was effectively used to detect and monitor potential drug-induced toxicity in SSPE patients. The analyte was extracted from human plasma using liquid-liquid extraction. Chromatographic separation was carried out on a C18 (50 mm x 2.1 mm x 3 µm) column with acetonitrile/0.2% formic acid- water (50/50, v/v)) isocratic mobile phase at a flow rate of 0.40 mL/min. It was studied in mass spectrometry in positive mode by electrospray ionisation technique and aprepitant was detected at 535.20 m/z. The retention time for the aprepitant was 2.70 min, and the total retention time was 4.8 min. The linear concentration range was 0.0125-3.00 µg/mL (r=0.9976), LOD and LOQ values were 0.01 µg/mL and 0.03 µg/mL, respectively. The developed method was successfully used for the determination of aprepitant concentration in plasma samples from SSPE patients. The developed and validated method is selective, sensitive and rapid. It can be safely and routinely used for aprepitant detection in preclinical and clinical studies.

Keywords

Aprepitant , Determination , LC-MS , Subacute Sclerosing Panencephalitis , Human plasma

Ethical Statement

The study was approved by regional ethical standards committees on human experimentation (26247029-514-04-02).

Supporting Institution

TUBITAK

Project Number

This study was funded by Scientific and Technological Research Council of Turkey (TUBITAK), 114S193.

Thanks

The authors thank subacute sclerosing panencephalitis patients and parents.

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