Arzneimittelforschung 2012; 62(12): 661-665
DOI: 10.1055/s-0032-1330019
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Fluorescence Detection of Etoposide-loaded Nanoparticles by HPLC and Pharmacokinetics Study

H.-Z. Yang
1   Department of Respiratory, Changsha Central Hospital, Changsha, China
2   Department of Clinical Pharmacology, Shanghai MercyTech Co., Ltd, Shanghai, China
,
L. Liu
2   Department of Clinical Pharmacology, Shanghai MercyTech Co., Ltd, Shanghai, China
,
X. Xu
2   Department of Clinical Pharmacology, Shanghai MercyTech Co., Ltd, Shanghai, China
› Author Affiliations
Further Information

Publication History

received 08 October 2012

accepted 21 October 2012

Publication Date:
28 November 2012 (online)

Abstract

Background:

A simple HPLC with fluorescence detection method was developed for determination and pharmacokinetic study of Etoposide in dog plasma.

Methods:

Plasma sample pretreatment involved liquid-liquid extraction of 500 µL plasma. The chromatographic separation was carried out on a Gemini C18 column with a mixture of methanol (A) and water (B) (0~5 min, volume of A was 45–50%, 5~10 min, volume of A was 50–90%) used as mobile phase at a flow rate of 0.4 ml/min.

Results:

These results indicated that the accuracy and precision of the current assay were within the recommendations for assay validation as stipulated in “Guidance for Industry: Bioanalytical Method Validation”. Etoposide nanoparticles and injection pharmacokinetic parameters were as follows: T1/2, 2.26 (0.71) and 1.74 (0.43) h;Cmax, 13.24 (5.32) and 8.12 (3.61) µg/ml; AUC0-t, 41.32 (7.33) and 16.53 (4.12) µg · ml − 1 · h; AUC0–∞, 49.54 (9.62) and 19.64 (8.22) µg · ml − 1 · h; MRT, 3.13 (0.54) and 2.06 (0.33) h and CL 7.35 (1.53) and 12.61 (2.22), respectively.

Conclusion:

This method was fully validated and successfully applied to a preclinical pharmacokinetic study of Etoposide in dogs after i. v. drip administration.

 
  • References

  • 1 Debien E, Hervouet E, Gautier F et al. ABT-737 and/or folate reverse the PDGF-induced alterations in the mitochondrial apoptotic pathway in low-grade glioma patients. Clin Epigenetics 2011; 2: 369-381
  • 2 Lawson MH, Cummings NM, Rassl DM et al. Two novel determinants of etoposide resistance in small cell lung cancer. Cancer Res 2011; 71: 4877-4887
  • 3 Zatloukal P, Cardenal F, Szczesna A et al. A multicenter international randomized phase III study comparing cisplatin in combination with irinotecan or etoposide in previously untreated small-cell lung cancer patients with extensive disease. Ann Oncol 2010; 21: 1810-1816
  • 4 Sadzuka Y, Hirota S, Sonobe T et al. Intraperitoneal administration of doxorubicin encapsulating liposomes against peritoneal dissemination. Toxicol Lett 2000; 116: 51-59
  • 5 Koga S, Hamazoe R, Maeta M et al. Prophylactic therapy for peritoneal recurrence of gastric cancer by continuous hyperthermic peritoneal perfusion with mitomycin C. Cancer 1988; 61: 232-237
  • 6 de La Motte Rouge T, Pautier P, Duvillard P et al. Survival and reproductive function of 52 women treated with surgery and bleomycin, etoposide, cisplatin (BEP) chemotherapy for ovarian yolk sac tumor. Ann Oncol 2008; 19: 1435-1441
  • 7 Bruzzone M, Centurioni MG, Giglione P et al. Second-line treatment with intravenous gemcitabine and oral etoposide in platinum-resistant advanced ovarian cancer patients: results of a phase II study. Oncology 2011; 80: 238-246
  • 8 Chamberlain M. Recurrent brainstem gliomas treated with oral VP-16. J Neurooncol 1993; 15: 133-139
  • 9 Ashley D, Meier L, Kerby T et al. Response of recurrent medulloblastoma to low-dose oral etoposide. J Clin Oncol 1996; 14: 1922-1927
  • 10 Reddy LH, Adhikari JS, Dwarakanath BS et al. Tumoricidal effects of etoposide incorporated into solid lipid nanoparticles after intraperitoneal administration in Dalton’s lymphoma bearing mice. AAPS J 2006; 8: 254-262
  • 11 Reddy LH, Murthy RS. Etoposide-loaded nanoparticles made from glyceride lipids: formulation, characterization, in vitro drug release, and stability evaluation. AAPS PharmSciTech 2005; 6: 158-166
  • 12 Reddy LH, Sharma RK, Chuttani K et al. Etoposide-incorporated tripalmitin nanoparticles with different surface charge: formulation, characterization, radiolabeling, and biodistribution studies. AAPS J 2004; 6: 23
  • 13 Chen CL, Uckun FM. Highly sensitive liquid chromatography-electrospray mass spectrometry (LC-MS) method for the determination of etoposide levels in human serum and plasma. J Chromatogr B Biomed Sci Appl 2000; 744: 91-98
  • 14 Freitas C, Muller RH. Spray-drying of solid lipid nanoparticles(SLN). Eur J Pharm Biopharm 1998; 46: 145-151