A high-performance liquid chromatography–tandem mass spectrometry method for the clinical combination study of carboplatin and anti-tumor agent eribulin mesylate (E7389) in human plasma

DesJardins, Christopher; Saxton, Phil; Lu, Song; Li, Xiaofang; Rowbottom, Christopher; Wong, Y. Nancy

doi:10.1016/j.jchromb.2008.09.013

Cited by 25 publications

(33 citation statements)

References 16 publications

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“…Plasma and urine concentrations of eribulin were determined using validated liquid chromatography/mass spectrometry/mass spectrometry methods (9). Analysis of eribulin (in freebase equivalents) in human plasma and urine was done using liquid chromatography/mass spectrometry/mass spectrometry on a Micromass Quattro Ultima (Micromass Limited) and an API4000 (Applied Biosystems) triple quadrupole mass spectrometer, respectively, under positive ion mode.…”

Section: Translational Relevancementioning

confidence: 99%

A Phase I Study of Eribulin Mesylate (E7389), a Mechanistically Novel Inhibitor of Microtubule Dynamics, in Patients with Advanced Solid Malignancies

Goel

Mita²,

Mita³

et al. 2009

Clinical Cancer Research

137

125

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Purpose: Eribulin mesylate (E7389), a non-taxane microtubule dynamics inhibitor, is a structurally simplified, synthetic analogue of halichondrin B that acts via a mechanism distinct from conventional tubulin-targeted agents. This phase I study determined the maximum tolerated dose (MTD) and pharmacokinetics of eribulin administered on a 3 of 4 week schedule in patients with advanced solid malignancies. Experimental Design: Patients received eribulin mesylate (1-hour i.v. infusion) on days1, 8, and 15 of a 28-day cycle. Dosing began at 0.25 mg/m 2 with escalation guided by dose-limiting toxicities (DLT). MTD, DLTs, safety, pharmacokinetics, and antitumor activity were characterized. Results:Thirty-two patients received eribulin mesylate (0.25, 0.5, 0.7, 1.0, or 1.4 mg/m 2 ). Neutropenia was the principal DLT: At 1.4 mg/m 2 , two patients experienced grade 4 neutropenia, one of whom also developed grade 3 fatigue; three additional patients experienced grade 3 neutropenia and were not treated during cycle 1on day 15. Therefore, the MTD was 1.0 mg/m 2 . Fatigue (53% overall, 13% grade 3, no grade 4), nausea (41%, all grade 1/2), and anorexia (38% overall, 3% grade 3, no grade 4) were the most common eribulin-related adverse events. Eight patients reported grade 1/2 neuropathy (no grade 3/4). Eribulin pharmacokinetics were dose-proportional over the dose range studied. One patient (cervical cancer) achieved an unconfirmed partial response lasting 79 days. Ten patients reported stable disease. Conclusions: Eribulin mesylate, given on days 1, 8, and 15 of a 28-day cycle, exhibits manageable tolerability at 1.0 mg/m 2 with further dose escalation limited by neutropenia and fatigue.

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Section: Translational Relevancementioning

confidence: 99%

A Phase I Study of Eribulin Mesylate (E7389), a Mechanistically Novel Inhibitor of Microtubule Dynamics, in Patients with Advanced Solid Malignancies

Goel

Mita²,

Mita³

et al. 2009

Clinical Cancer Research

137

125

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“…24,48, and 72 h after the start of infusion on day 1 of cycle 1. Plasma and urine concentrations of eribulin were measured using a validated liquid chromatography tandem mass spectrometry method, described in detail elsewhere (16).…”

Section: Translational Relevancementioning

confidence: 99%

Phase I Study of Eribulin Mesylate Administered Once Every 21 Days in Patients with Advanced Solid Tumors

Tan

Rubin

Walton

et al. 2009

Clinical Cancer Research

132

102

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Purpose: To evaluate the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), and pharmacokinetics of eribulin mesylate (E7389), a halichondrin B analogue, administered every 21days in patients with advanced solid tumors. Experimental Design: Eribulin mesylate was given as a 1-hour infusion every 21days at doses of 0.25, 0.5, 1, 2, 2.8, and 4 mg/m 2 .The MTD was identified using an accelerated titration design. The pharmacokinetics of eribulin were evaluated in the plasma and urine with the first dose. Results: Twenty-one patients were enrolled. At 4 mg/m 2 , three patients experienced a DLT of febrile neutropenia on day 7. The dose level was reduced to 2.8 mg/m 2 where two of three patients experienced dose-limiting febrile neutropenia. Six additional patients were enrolled at 2 mg/m 2 (seven patients in total received this dose) and one of these patients experienced a neutropenic DLT. The MTD of eribulin mesylate was therefore 2 mg/m 2 . Nonhematologic toxicities included alopecia, fatigue, anorexia, and nausea. Pharmacokinetic analysis showed linear kinetics for eribulin over the dose range studied and a terminal half-life of 2 days. The plasmaconcentration-time profile exhibited a rapid distribution phase followed by a slow elimination phase. Drug clearance was nonrenal. One patient with non^small cell lung cancer achieved an unconfirmed partial response and 12 patients had stable disease. Conclusions: Eribulin mesylate administered as a 1-hour infusion every 21 days has a manageable toxicity profile at 2 mg/m 2 , with further dose escalation limited by neutropenia.

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“…[269][270][271] The introduction of an additional derivatisation step improved sensitivity (up to a factor of 100) with LC-UV methods. 272,273 Better LOQ's, between 2 and 25 ng mL −1 , were reached with LC-MS. [274][275][276][277][278] However, the technique of choice for the detection of platinum derivatives was undoubtedly inductively coupled plasma mass spectrometry (ICP-MS). ICP-MS coupled to a separation technique, [279][280][281][282][283][284]285 or not, 21,286,287 is characterised by an excellent LOQ, in the range 0.1 to 1 µg mL −1 .…”

Section: 233-237mentioning

confidence: 99%

“…This is because this analytical technique requires a sample degradation step via photolysis digestion. 113,[288][289][290] For the separation step, different chromatographic supports were used, including reversed phase columns, 269,270,277,281,278 ion exchange columns, 275 HILIC support 285 or cellulose based columns for the enantiomer resolution of oxaliplatin. 291 CE was also reported as a promising technique for the separation of platinum derivatives.…”

Section: 233-237mentioning

confidence: 99%

Antineoplastic drugs and their analysis: a state of the art review

Guichard

Guillarme

Bonnabry

et al. 2017

Analyst

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The number of patients suffering from cancer is constantly increasing and, consequently, the number of different chemotherapy treatments administered is increasing. Given the high reactivity and toxicity of antineoplastic drugs, analytical methods are required in all pharmaceutical fields, from drug development to their elimination in wastewater; including formulation quality control, environment and human exposure and therapeutic drug monitoring. The aim of this paper is to provide an overview of the analytical methods available for the determination of antineoplastic drugs in different matrices such as pharmaceutical formulations, biological and environmental samples. The applicability and performance of the reported methods will be critically discussed, with focus on the most commonly used antineoplastic drugs. Only conventional compounds and small molecules for targeted therapy will be considered in the present review.

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A high-performance liquid chromatography–tandem mass spectrometry method for the clinical combination study of carboplatin and anti-tumor agent eribulin mesylate (E7389) in human plasma

Cited by 25 publications

References 16 publications

A Phase I Study of Eribulin Mesylate (E7389), a Mechanistically Novel Inhibitor of Microtubule Dynamics, in Patients with Advanced Solid Malignancies

A Phase I Study of Eribulin Mesylate (E7389), a Mechanistically Novel Inhibitor of Microtubule Dynamics, in Patients with Advanced Solid Malignancies

Phase I Study of Eribulin Mesylate Administered Once Every 21 Days in Patients with Advanced Solid Tumors

Antineoplastic drugs and their analysis: a state of the art review

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