Research ArticleOpen AccessGoogle Scholar indexed
Nonclinical Study of the Active Components of Doxorubicin Hydrochloride Liposome Injection <i>in Vivo</i>
NMPA Key Laboratory for Bioequivalence Research of Generic Drug Evaluation, Shenzhen Institute for Drug Control, Shenzhen, China
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China
NMPA Key Laboratory for Bioequivalence Research of Generic Drug Evaluation, Shenzhen Institute for Drug Control, Shenzhen, China
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China
- 1 NMPA Key Laboratory for Bioequivalence Research of Generic Drug Evaluation, Shenzhen Institute for Drug Control, Shenzhen, China
- 2 State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China
- 3 NMPA Key Laboratory for Bioequivalence Research of Generic Drug Evaluation, Shenzhen Institute for Drug Control, Shenzhen, China
- 4 State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China
- 5 State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China
- 6 State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China
- 7 State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China
Pharmacology & Pharmacy·Volume 14 (2023)·Pages 363–375·Published 6 September 2023·DOI10.4236/pp.2023.149023
Copy link · social · email
Abstract
Objectives: A non-clinical study was performed to establish a LC-MS/MS method to determine the in vivo active components of doxorubicin hydrochloride liposome injection in the plasma of Sprague-Dawley rats. Methods: Ten male SD rats were administered tail vein with a single dose of 10 mg/kg, and the concentrations of doxorubicin hydrochloride in plasma, heart, liver, spleen, lung, and kidney were determined by liquid chromatography-tandem mass spectrometry, and the pharmacokinetic parameters were calculated. Results: The final concentration of doxorubicin hydrochloride ranged from 500 ng/mL to 250,000 ng/mL, and the lower limit of quantification was 500 ng/mL; the main pharmacokinetic parameters: T 1/2 was (19.282 ± 10.305) h, C max was (118514.828 ± 26155.134) ng/mL, AUC 0-24 and AUC 0-∞ were (1216659.205 ± 192706.268) ng/mL ⋅ h and (2082244.523 ± 860139.487) ng/mL ⋅ h, MRT 0-24 and MRT 0-∞ were (9.237 ± 0.423) h and (26.52 ± 14.015) h, respectively, and clearance (CL) was (0.005 ± 0.002) mL/h ⋅ ng. Conclusions: The method is simple, rapid, and sensitive, which can be used for the determination of doxorubicin hydrochloride concentration in the plasma of SD rats and pharmacokinetic non-clinical studies.
KeywordsDoxorubicin Hydrochloride LiposomesPharmacokineticsLC-MS/MS
- Bonadonna, G., Monfardini, S., De Lena, M. and Fossati-Bellani, F. (1969) Clinical Evaluation of Adriamycin, A New Antitumour Antibiotic. British Medical Journal, 3, 503-506. https://doi.org/10.1136/bmj.3.5669.503
- Gregoriadis, G. and Ryman, B.E. (1971) Liposomes as Carriers of Enzymes or Drugs: A New Approach to the Treatment of Storage Diseases. The Biochemical Journal, 124, 58 p. https://doi.org/10.1042/bj1240058P
- Abu, L.A., Ishida, T. and Kiwada, H. (2009) Recent Advances in Tumor Vasculature Targeting Using Liposomal Drug Delivery Systems. Expert Opinion on Drug Delivery, 6, 1297-1309. https://doi.org/10.1517/17425240903289928
- Eliaz, R.E. and Szoka, F.J. (2001) Liposome-Encapsulated Doxorubicin Targeted to CD44: A Strategy to Kill CD44-Overexpressing Tumor Cells. Cancer Research, 61, 2592-2601.
- Bielack, S.S., Erttmann, R., Kempf-Bielack, B. and Winkler, K. (1996) Impact of Scheduling on Toxicity and Clinical Efficacy of Doxorubicin: What Do We Know in the Mid-Nineties. European Journal of Cancer, 32, 1652-1660. https://doi.org/10.1016/0959-8049(96)00177-3
- Chen, Q., Tong, S., Dewhirst, M.W. and Yuan, F. (2004) Targeting Tumor Microvessels Using Doxorubicin Encapsulated in a Novel Thermosensitive Liposome. Molecular Cancer Therapeutics, 3, 1311-1317. https://doi.org/10.1158/1535-7163.1311.3.10
- Singh, R. and Lillard, J.J. (2009) Nanoparticle-Based Targeted Drug Delivery. Experimental and Molecular Pathology, 86, 215-223. https://doi.org/10.1016/j.yexmp.2008.12.004
- Rappold, B.A. (2022) Review of the Use of Liquid Chromatography-Tandem Mass Spectrometry in Clinical Laboratories: Part II—Operations. Annals of Laboratory Medicine, 42, 531-557. https://doi.org/10.3343/alm.2022.42.5.531
- Liu, M. and He, R. (2022) Current Status of Research on Human Bioequivalence of Doxorubicin Hydrochloride Liposome Injection and Related Considerations at Home and Abroad. Chinese Journal of Clinical Pharmacology, 38, 1972-1976.
- Harahap, Y., Suryadi, H. and Anarta, A. (2020) Development and Validation of Doxorubicin Hydrochloride and Doxorubicinol Quantification Method in Dried Blood Spot by Liquid Chromatography-Tandem Mass Spectrometry. Journal of Pharmacy & Bioallied Sciences, 12, 406-412. https://doi.org/10.4103/JPBS.JPBS_167_20
- Fleury-Souverain, S., Maurin, J., Guillarme, D., Rudaz, S. and Bonnabry, P. (2022) Development and Application of a Liquid Chromatography Coupled to Mass Spectrometry Method for the Simultaneous Determination of 23 Antineoplastic Drugs at Trace Levels. Journal of Pharmaceutical and Biomedical Analysis, 221, 115034. https://doi.org/10.1016/j.jpba.2022.115034