Determination of free and total vincristine in human plasma after intravenous administration of vincristine sulfate liposome injection using ultra-high performance liquid chromatography tandem mass spectrometry

Yang, Fen; Wang, Hongyun; Liu, Ming; Hu, Pei; Jiang, Ji

doi:10.1016/j.chroma.2012.12.026

Cited by 26 publications

(14 citation statements)

References 17 publications

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“…Thus, it was anticipated that VCR is released from the liposome to increase the concentration of VCR in tumor site and to decrease the concentration of free drug in plasma, then the vast majority of drug present in circulation remains entrapped with liposomes. In order to confirm this hypothesis and better understand the release character of VCR from liposome of VSLI in human being, we developed an SPE method to separate the F-VCR from the liposomal VCR in plasma and the concentration of F-VCR was determined (Yang et al, 2013). Based on these data, we observed that the VCR was not released at constant speed because multiple peaks appeared in the plasma F-VCR concentration-time profile.…”

Section: Discussionmentioning

confidence: 99%

“…The plasma concentration of F-VCR and T-VCR and the urine VCR concentration was determined using the ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) system (Waters Corporation, Milford, MA, United States) with vinblastine sulfate used as the internal standard (IS) as previously described by our team (Yang et al, 2013, 2015). The compounds were detected as doubly charged ions and the multiple reaction monitor (MRM) transitions of VCR and the IS were m/z 413.2 → 353.2 and m/z 406.2 → 271.6, respectively.…”

Section: Methodsmentioning

confidence: 99%

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Pharmacokinetic Behavior of Vincristine and Safety Following Intravenous Administration of Vincristine Sulfate Liposome Injection in Chinese Patients With Malignant Lymphoma

Yang

Jiang

et al. 2018

Front. Pharmacol.

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Objective: This phase Ia study was designed to assess the pharmacokinetic (PK) characters of free vincristine (F-VCR, refer to as non-liposomal VCR and VCR released from liposome) and total vincristine (T-VCR, the sum of both liposomal VCR and F-VCR), urinary excretion and safety of intravenous administration of vincristine sulfate liposomes injection (VSLI) in Chinese patients with malignant lymphoma and compare the results with those for conventional vincristine sulfate injection (VSI).Methods: In the phase Ia, randomized, open-label, two sequence cross-over study, patients from one group were exposed to treatment 1 including cytoxan (cyclophosphamide power injection), hydroxyrubicin (adriamycin power injection), oncovin (VSI), and prednisone tablets (standard CHOP scheme) before crossed over to treatment 2 (modified CHOP scheme in which VSI was replaced with VSLI). Patients from another group received treatments in reverse order.Results: In this phase Ia study, a total of eight subjects participated. VCR elimination from the circulation after injection of VSLI was characterized by a significantly increased maximum concentration (Cmax, 86.6 ng/mL) and plasma area under the plasma concentration-time curve from zero to infinity (AUC0-Inf, 222.1 ng/mL h), markedly decreased distribution volume (Vz, 224.1 L) and plasma clearance (CL, 8.9 L/h) compared to lower Cmax (26.6 ng/mL) and AUC0-Inf (95.1 ng/mL h), larger Vz (688.8 L) and CL (22.1 L/h) for VSI. The small proportion of F-VCR following infusion of VSLI in circulation was reflected by very low Cmax (1.8 ng/mL) and AUC0-Inf (50.5 ng/mL h). Less than 3% of the administered dose of VSLI was excreted in urine and the extent was similar to that for VSI. The elimination percentage of 40–21–14% for VSI changed to 6.2–24–39% for VSLI at intervals of 0–5, 5–13 and 13–25 h, respectively. Significant difference of toxicity between VSLI and VSI was not observed.Conclusion: VSLI exhibits higher AUC0-Inf of T-VCR, lower CL and Vz compared with VSI. VSLI was well tolerated, maybe due to the markedly decreasing AUC0-Inf of F-VCR. The majority of VCR was enveloped in liposome and VCR was released gradually from liposome following injection of VSLI. Liposomal encapsulation of VCR does not alter the route and extent of VCR excretion in urine.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Pharmacokinetic Behavior of Vincristine and Safety Following Intravenous Administration of Vincristine Sulfate Liposome Injection in Chinese Patients With Malignant Lymphoma

Yang

Jiang

et al. 2018

Front. Pharmacol.

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“…Vincristine, a natural vinca alkaloid, was first derived from the leaves of C. roseus[34-36] and has been used in tumor therapy since the 1960s as a cell cycle-specific (M-phase) antineoplastic agent. [18, 29, 34-38] The alkaloid can bind to tubulin, causing microtubule depolymerization, metaphase arrest, and apoptosis in cells undergoing mitosis.…”

Section: Vincristinementioning

confidence: 99%

Drug Delivery Systems and Combination Therapy by Using Vinca Alkaloids

Lee¹,

Huang²,

Yang³

et al. 2015

CTMC

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Developing new methods for chemotherapy drug delivery has become a topic of great concern. Vinca alkaloids are among the most widely used chemotherapy reagents for tumor therapy; however, their side effects are particularly problematic for many medical doctors. To reduce the toxicity and enhance the therapeutic efficiency of vinca alkaloids, many researchers have developed strategies such as using liposome-entrapped drugs, chemical- or peptide-modified drugs, polymeric packaging drugs, and chemotherapy drug combinations. This review mainly focuses on the development of a vinca alkaloid drug delivery system and the combination therapy. Five vinca alkaloids (eg, vincristine, vinblastine, vinorelbine, vindesine, and vinflunine) are reviewed.

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“…Therefore, it is important to verify how much drug is encapsulated within nanomedicines to ensure their safe and proper usage. Many methods for evaluating the encapsulated drugs have been reported [8][9][10][11][12][13][14][15][16], and several reviews have been published [17,18].…”

Section: Introductionmentioning

confidence: 99%

“…The encapsulated drug is then extracted by collapsing the nanoparticles and measured [8][9][10][11][12][13]. Although many nanoparticle purification methods (such as ultracentrifugation, dialysis, and ultrafiltration) have been developed, it remains difficult to remove interferents from the dispersed nanoparticle solution.…”

Section: Introductionmentioning

confidence: 99%

Rapid evaluation of the quantity of drugs encapsulated within nanoparticles by high-performance liquid chromatography in a monolithic silica column

2015

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Drug-containing nanoparticles, the foundation of nanomedicine, provide promise for the safe and effective delivery of drugs to their targets. In this study, we developed a simple method to determine the relative quantities of nanoparticle-encapsulated drugs by HPLC using a commercially available monolithic silica column. Amphotericin B- and irinotecan-containing nanoparticles produced nearly simultaneous elution peaks (~7 min), suggesting that elution was largely driven by hydrodynamic effects and was relatively unaffected by differences in the encapsulated drug. A good correlation was observed between the intensity of the nanoparticle peak and the relative quantity of encapsulated drug. We used our method to characterize the effects of drug quantity and nanoparticle size on drug encapsulation rates within the nanoparticles. Encapsulation increased with increasing quantities of the drug in the preparation solution. This effect was greater for irinotecan than for amphotericin B. Although absolute encapsulation also increased with increasing nanoparticle size, encapsulation efficiency decreased. Thus, the monolith column is suitable for evaluating nanomedicine quality and may be used to evaluate many kinds of nanomaterials. Graphical Abstract Evaluation method of quantity of drug encapsulated within nanoparticles was developed. The method can be applicable for a rapid quality assurance of nanomedicine.

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Determination of free and total vincristine in human plasma after intravenous administration of vincristine sulfate liposome injection using ultra-high performance liquid chromatography tandem mass spectrometry

Cited by 26 publications

References 17 publications

Pharmacokinetic Behavior of Vincristine and Safety Following Intravenous Administration of Vincristine Sulfate Liposome Injection in Chinese Patients With Malignant Lymphoma

Pharmacokinetic Behavior of Vincristine and Safety Following Intravenous Administration of Vincristine Sulfate Liposome Injection in Chinese Patients With Malignant Lymphoma

Drug Delivery Systems and Combination Therapy by Using Vinca Alkaloids

Rapid evaluation of the quantity of drugs encapsulated within nanoparticles by high-performance liquid chromatography in a monolithic silica column

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