Sensitive method for the determination of vincristine in human serum by high-performance liquid chromatography after on-line column-extraction

Bloemhof, H.; Dijk, Karen Nanette van; Graaf, Siebold S.N. de; Vendrig, D. E. M. M.; Uges, Donald

doi:10.1016/0378-4347(91)80481-q

Cited by 35 publications

(17 citation statements)

References 5 publications

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“…Vincristine plasma concentration was measured by HPLC with electrochemical detection (28). The sensitivity of the assay was 0.48 g/L, and coefficients of variation were 6.2% (0.48 g/L) and 4.2% (18.40 g/L) in within-day precision studies, and 10.3% (0.48 g/L) and 8.5% (18.40 g/L) in between-day studies.…”

Section: Patientsmentioning

confidence: 99%

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Pharmacokinetics of Vincristine Monotherapy in Childhood Acute Lymphoblastic Leukemia

Groninger¹,

Boer²,

Koopmans³

et al. 2002

Pediatr Res

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We studied vincristine pharmacokinetics in 70 children newly diagnosed with acute lymphoblastic leukemia, after a single dose of vincristine as monotherapy. Vincristine plasma concentrations were measured by HPLC analysis. A two-compartment, firstorder pharmacokinetic model was fitted to the data by maximum a posteriori parameter estimation. In this group of children pharmacokinetic factors were highly variable: median (25th and 75th percentiles) total body clearance, 228 (128 -360) Vincristine, one of the naturally occurring vinca alkaloids extracted from the leaves of the periwinkle plant Catharanthus roseus, continues to play a key role in the treatment of childhood ALL since its introduction in 1962 (1). Vincristine exerts an antimitotic effect (2-4) and induces apoptosis in various hematologic cell lines (5-8). Its antileukemic effect in vivo is determined by both variability in exposure of the leukemic cells and variability in sensitivity of the cells to the effect of vincristine. In vitro sensitivity of leukemic cells has been well studied (9), but the variability in exposure of leukemic cells in vivo has received less attention. Therefore, we studied vincristine pharmacokinetics in children newly diagnosed with ALL, after a single dose of vincristine.Vincristine-induced cell kill in a human lymphoblastic leukemia cell line was proportional to saturation of cellular binding sites (10), suggesting that the concentration of vincristine to which the cell is exposed is an important determinant of the antileukemic effect of vincristine. In vitro, vincristine accumulates in cells to concentrations as high as 500 times extracellular concentrations and is slowly released from the cells after restoration in drug-free medium (11, 12). Tissue distribution of vincristine was studied with 3 H-labeled vincristine in the rat and revealed accumulation in spleen, adrenal and thyroid glands, large and small intestines, heart, lung, kidney, liver, and marrow. Penetration in rat eye, fat, and brain tissue and in human cerebrospinal fluid appears to be very poor (13)(14)(15).The first pharmacokinetic studies on vincristine in man were performed when 3 H-labeled vincristine became available, 15 y after the introduction of vincristine in clinical practice. It was found that urinary excretion accounts for up to 12% of excreted radioactivity (16, 17). The biliary system appeared to be the principal route of excretion (13, 18 -20

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Section: Patientsmentioning

confidence: 99%

“…The development of an HPLC method for the measurement of vincristine concentrations in biologic fluids made it possible to study vincristine pharmacokinetics with greater specificity than the previously used RIA (25)(26)(27)(28). CL appeared to be faster in children than in adults (mean CL, 431 and 189 mL·min Ϫ1 ·m Ϫ2 , respectively) (29,30).…”

mentioning

confidence: 99%

Pharmacokinetics of Vincristine Monotherapy in Childhood Acute Lymphoblastic Leukemia

Groninger¹,

Boer²,

Koopmans³

et al. 2002

Pediatr Res

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“…For the determination of vincristine in plasma, radioimmunoassay (Nelson, 1982), HPLC (Koopmans et al, 2001;Embree et al, 1997;Bloemhof et al, 1991) and liquid chromatographicmass spectrometric methods (Dennison et al, 2008;Lee et al, 2007;Skolnik et al, 2006;Corona et al, 2008;Guilhaumou et al, 2010) have been reported. Some of these methods used a large volume of plasma sample (0.3-4 mL) or needed longer chromatographic run time (8 min), while others employed complicated extraction processes (on-line extraction step after precipitation).…”

Section: Introductionmentioning

confidence: 99%

An LC‐MS/MS method for simultaneous determination of vincristine and verapamil in rat plasma after oral administration of a dual agent formulation

Ling

Zhang

Sun

et al. 2010

Biomedical Chromatography

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A rapid and sensitive method for simultaneous determination of vincristine and verapamil in rat plasma was first developed and validated, using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) in multiple reaction monitoring (MRM) mode via electrospray ionization (ESI). The method, which required a small sample volume (25 µL) of plasma, was linear in the concentration range of 0.5-500 ng/mL for vincristine and 0.1-100.0 ng/mL for verapamil. Finally, the method was successfully employed in a pharmacokinetic study of vincristine and verapamil in rats after an oral administration of a dual-agent formulation containing vincristine and verapamil.

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“…In the literature there was no consensus about storage of samples at À208C 12,14,16,20,21 or À708C, 17,18,22,23,26,27 thus experiments at both temperatures were executed. Both vincristine and actinomycin-D were stable in human EDTA plasma for at least three freeze/thaw cycles at both temperatures, and in human EDTA plasma at ambient temperatures for up to 6 h. Furthermore, vincristine and actinomycin-D were stable up to 23 days in the final extract at nominally 2-88C.…”

Section: Validationmentioning

confidence: 99%

Validated assay for the simultaneous quantification of total vincristine and actinomycin‐D concentrations in human EDTA plasma and of vincristine concentrations in human plasma ultrafiltrate by high‐performance liquid chromatography coupled with tandem mass spectrometry

Damen

Israëls

Caron

et al. 2009

Rapid Comm Mass Spectrometry

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A sensitive, specific and efficient high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) assay for the simultaneous determination of total vincristine and actinomycin-D concentrations in human plasma and an assay for the determination of unbound vincristine are presented. Electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI) and heated electrospray ionization (H-ESI) were tested as ionization interfaces. For reasons of robustness ESI was chosen followed by tandem mass spectrometry (ESI-MS/MS). For the plasma assay a 30 microL aliquot was protein precipitated with acetonitrile/methanol (50:50, v/v) containing the internal standard vinorelbine and 10 microL volumes were injected onto the HPLC system. To determine unbound vincristine, ultrafiltrate was produced from plasma using 30 kDa centrifugal filter units. The plasma ultrafiltrate was mixed with methanol (50:50, v/v), internal standard vinorelbine was added and 20 microL aliquots were injected onto the HPLC system. Separation was achieved on a 50x2.1 mm i.d. Xbridge C18 column using 1 mM ammonium acetate/acetonitrile (30:70, v/v) adjusted to pH 10.5 with ammonia, run in a gradient with methanol at a flow rate of 0.4 mL/min. HPLC run time was 6 min. The assay quantifies in plasma vincristine from 0.25 to 100 ng/mL and actinomycin-D from 0.5 to 250 ng/mL using plasma sample volumes of only 30 microL. Vincristine in plasma ultrafiltrate can be quantified from 1 to 100 ng/mL. Validation results demonstrate that vincristine and actinomycin-D can be accurately and precisely quantified in human plasma and plasma ultrafiltrate with the presented methods. The assays are now in use to support clinical pharmacological studies in children treated with vincristine and actinomycin-D.

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Sensitive method for the determination of vincristine in human serum by high-performance liquid chromatography after on-line column-extraction

Cited by 35 publications

References 5 publications

Pharmacokinetics of Vincristine Monotherapy in Childhood Acute Lymphoblastic Leukemia

Pharmacokinetics of Vincristine Monotherapy in Childhood Acute Lymphoblastic Leukemia

An LC‐MS/MS method for simultaneous determination of vincristine and verapamil in rat plasma after oral administration of a dual agent formulation

Validated assay for the simultaneous quantification of total vincristine and actinomycin‐D concentrations in human EDTA plasma and of vincristine concentrations in human plasma ultrafiltrate by high‐performance liquid chromatography coupled with tandem mass spectrometry

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