Determination of Nitrosourea Compounds in Brain Tissue by Gas Chromatography and Electron Capture Detection

Hassenbusch, Samuel J.; Colvin, O. Michael; Anderson, James H.

doi:10.1002/jps.2600840711

Cited by 3 publications

(5 citation statements)

References 13 publications

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“…A method for the efficient extraction of BCNU from plasma matrix was developed based on reported data. [5,8,10,11] A variety of solvents including acetonitrile, methanol, ethyl acetate=hexane, and hexane=isopropyl ether were evaluated, and the extraction with hexane=isopropyl ether proved to be optimal and led to 81.3% sample recovery. The BCNU solutions were tested in the range of 0.2 to 10.2 mg=mL (r 2 ¼ 0.9999) with 0.2 mg=mL as lower limit of quantitation (S=N ¼ 17:1) (RSD ¼ 17.8%, n ¼ 6).…”

Section: Resultsmentioning

confidence: 98%

“…[5,14,17] Analysis of BCNU has been a challenge because of its instability in solution. [6] As mentioned in the introduction, there are several analytical methods in the literature which either require derivatization or the use of deuterated isotopes.…”

Section: Resultsmentioning

confidence: 99%

“…[10] and gas chromatography coupled with various detectors including mass spectrometry and an electron capture detector. [5,11] These reported methods are either non-selective or require a derivatization treatment, which makes them unsuitable for selective high throughput analysis.…”

Section: Introductionmentioning

confidence: 99%

“…[4] N,N 0 -bis (2-chloroethyl)-N-nitrosourea (BCNU ¼ carmustine) is an FDA approved antineoplastic agent for the treatment of malignant brain tumors and has been a mainstay of chemotherapy treatment for brain tumors for more than twenty years. [5] It decomposes under physiological conditions and one of the decomposition products (alkylating agent) is the proposed active molecule. [6,7] Previously reported analytical methods for the analysis of BCNU include a colorimetric assay, [8] high performance liquid chromatography coupled with a UV detector, [9] chemical ionization mass spectrometry analysis.…”

Section: Introductionmentioning

confidence: 99%

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A Simple and Sensitive Apci-Lc-MS Method for the Detection of the Antitumor Agent, Carmustine (Bcnu) in Rat Plasma

Kate

Kohl

Kerr

2010

Journal of Liquid Chromatography & Related Technologies

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& A simple and sensitive LC-MS method for the quantitative determination of the antitumor agent, N,N 0 -bis (2-chloroethyl)-N-nitrosourea (BCNU or carmustine), is described in this report. The method has been developed using an atmospheric pressure chemical ionization (APCI) probe on an ion trap mass spectrometer. A formate adduct ([M þ 45] À ) of BCNU was observed in the negative mode at 257.8 m=z and further confirmation for BCNU was obtained by observing the characteristic isotopic pattern in the mass spectrum, which indicated the compound contained two chlorine atoms. The extraction of BCNU from rat plasma with isopropyl ether:hexane (1:1) resulted in 81.3% of sample recovery. The limit of detection (LOD) calculated for the method was 1.25 ng (injected amount) using a standard solution of BCNU (S=N ¼ 9:1). Optimum linearity and reproducibility data were obtained for BCNU; r 2 ¼ 0.9999 (0.2 mg=mL to 10.2 mg=mL) with precision of (RSD) 6.4% at two different concentrations and accuracy of 92.3 and 102.4%.

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Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Simple and Sensitive Apci-Lc-MS Method for the Detection of the Antitumor Agent, Carmustine (Bcnu) in Rat Plasma

Kate

Kohl

Kerr

2010

Journal of Liquid Chromatography & Related Technologies

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“…This method has been employed also for the determination of BCNU in plasma [23][24][25] or CCNU in a mouse tumor tissue 26 . Other methods previously used in analysis of plasma or brain tissue containing BCNU or CCNU include gas chromatography with thermoionic N-P detection 27 , electron capture detection 28 , or mass spectrometric detection 29 . Attention was paid also to the analysis of sewage plant effluents, as cytostatic drugs may appear in clinical waste waters 30 .…”

mentioning

confidence: 99%

Voltammetric and amperometric determination of N-nitroso antineoplastic drugs at mercury and amalgam electrodes

Pecková

Vrzalová

Bencko

et al. 2009

Collect. Czech. Chem. Commun.

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Dedicated to the memory of Professor Jaroslav Heyrovský on the occasion of the 50th anniversary of the Nobel Prize for polarography.A hanging mercury drop electrode and a mercury meniscus modified silver solid amalgam electrode were used as electroanalytical sensors for voltammetric determination of antineoplastic drugs carmustine, lomustine and streptozotocin containing reducible N-nitroso groups. On the example of carmustine it was shown that its one-step reduction proceeds at substantially more negative potentials at amalgam electrode as compared with mercury electrode. Both electrodes offer satisfactory repeatability of current response (relative standard deviations < 5%) using DC voltammetry and differential pulse voltammetry. The achieved limits of determination lie mostly in the 10 -7 mol l -1 concentration range. The mentioned voltammetric methods were applied to determination of carmustine and lomustine in pharmaceutical formulations. Further, the mercury meniscus modified silver solid amalgam electrode was employed in a "wall-jet" amperometric detection cell in the determination of carmustine by flow injection analysis. Under optimized conditions (run electrolyte BrittonRobinson buffer of pH 7.0; flow rate 5.5 ml min -1 ; detection potential -1.5 V; injection volume 0.02 ml) the limit of quantitation 7.1 × 10 -6 mol l -1 was achieved.

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Transient cerebral hypoperfusion enhances intraarterial carmustine deposition into brain tissue

Joshi

Wang²,

Etu³

et al. 2007

J Neurooncol

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We hypothesized that bolus injections of lipid soluble chemotherapeutic drugs during transient cerebral hypoperfusion could significantly boost regional drug delivery. In the first two groups of New Zealand White rabbits we measured brain tissue carmustine concentrations after intravenous infusion, intraarterial infusion with normal perfusion, and after intraarterial injections during transient cerebral hypoperfusion. In the third group of animals we assessed the safety of the technique by assessing electroencephalographic changes for 6 h after flow arrest carmustine administration and subsequent histological examination. The brain tissue carmustine concentrations were fivefold to sevenfold higher when the drug was injected during cerebral hypoperfusion compared to a conventional intracarotid infusion (68.4 +/- 24.5 vs. 14.2 +/- 8.3 microg/g, n = 5 each, respectively, P < 0.0001). The brain tissue carmustine concentrations (y) were a linear function of the bolus dose (x) injected during cerebral hypoperfusion, y = 10.4 x x - 21 (R = 0.84, P < 0.001). Stable EEGs were recorded several hours after flow arrest carmustine exposure and histological examinations did not reveal any gross evidence of cerebral injury. Transient cerebral hypoperfusion during intraarterial bolus injection of carmustine significantly increases drug delivery. Clinical techniques that decrease CBF, such as, transient arterial occlusion by balloon tipped catheters, hyperventilation, hypothermia, induced hypotension, or transient circulatory arrest, could enhance intraarterial drug delivery to the brain. We believe that the mechanisms for improved drug delivery is the decrease in drug dilution by reduced or absent blood flow, decreased protein binding and a longer time for high concentrations of free drugs to transit through the blood brain barrier.

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Determination of Nitrosourea Compounds in Brain Tissue by Gas Chromatography and Electron Capture Detection

Cited by 3 publications

References 13 publications

A Simple and Sensitive Apci-Lc-MS Method for the Detection of the Antitumor Agent, Carmustine (Bcnu) in Rat Plasma

A Simple and Sensitive Apci-Lc-MS Method for the Detection of the Antitumor Agent, Carmustine (Bcnu) in Rat Plasma

Voltammetric and amperometric determination of N-nitroso antineoplastic drugs at mercury and amalgam electrodes

Transient cerebral hypoperfusion enhances intraarterial carmustine deposition into brain tissue

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