Development and validation of an LC-MS/MS method for the quantification of free and total doxorubicin in human plasma and its clinical application for a novel doxorubicin hydrochloride liposome injection in Chinese patients with breast cancer

• Autorzy: Zhang Keyu , Zhang Daqing , Ge Zhicheng , Qiu Feng

Identyfikatory

DOI

10.1556/1326.2023.01129

• Języki publikacji: EN

Abstrakty

EN

A novel doxorubicin hydrochloride liposome injection was prepared to reduce toxicity and side effects, as well as extend plasma half-life in the treatment of breast cancer. In this study, a rapid and sensitive bioanalytical method was developed and validated to characterize the pharmacokinetic profile of total and free doxorubicin in plasma of 3 Chinese patients after intravenous infusion of this injection. Plasma samples were prepared by protein precipitation for the determination of total doxorubicin, while solid phase extraction was used to determine free doxorubicin. After plasma sample pre-treatment, total and free concentrations were quantified individually using a validated LC-MS/MS method. The calibration curves were found to be linear in the range of 0.20–500.0 ng mL1 for total doxorubicin and in the range of 1.00–1,000 ng mL1 for free doxorubicin. The free concentrations in plasma were only one sixth to one quarter of the total levels. Liposomal doxorubicin had a longer apparent half-life (>50 h) than the non-targeted drug (<10 h) reported in the reference. and a lower volume of distribution. This novel injectable formulation steadily released free doxorubicin from liposomes over a long period of time to reduce cardiac toxicity and side effects, while ensuring a clinical curative effect.

Słowa kluczowe

EN

LC-MS/MS; solid-phase extraction; liposomal doxorubicin; breast cancer; pharmacokinetics

• Wydawca: University of Silesia in Katowice ; Akademiai Kiado
• Czasopismo: Acta Chromatographica
• Rocznik: 2024
• Tom: Vol. 36, no. 3
• Strony: 186--195
• Opis fizyczny: Bibliogr. 28 poz., rys., wykr.

Twórcy

autor

Zhang Keyu

• Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China

autor

Zhang Daqing

• Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China

autor

Ge Zhicheng

• Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China

autor

Qiu Feng

• Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China

• https://orcid.org/0000-0002-9945-0612

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