Modification of the 4-(p-nitrobenzyl) pyridine assay for measurement of melphalan and mechlorethamine in plasma

Skibba, Joseph L.; Collins, Fred G.

doi:10.1016/0160-5402(80)90034-0

Cited by 7 publications

(5 citation statements)

References 16 publications

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“…Many examples exist: phenylalanine mustards in blood; chlorambucil, sarcochlorine, mannomustine, and others in plasma and urine; mannitol myleran in urine and blood; bis(2-chloroethyl)methylamine in plasma, lymph, urine, or tissue homogenates; melphalan and mechlorethamine in plasma; and 3-[bis(2-chlorethyl)-carbohydrazide]-2,2,5,5-tetramethylpyroline-1-oxyl, a spin-labeled nitrogen mustard, and bioreductive diaziquones …”

Section: Uses Of the Nbp Methods And Alkylation Mechanismsmentioning

confidence: 99%

“…96 Skibba and Collins have also proposed some modifications for the detection of antineoplastic nitrogen mustards. 97 Additionally, after following the kinetics of the NBP alkylation reaction by a variety of alkylating agents, 98−100 Kawazoe concluded that temperature and pH must be carefully monitored 101 because of the lability of the reactants, and a pH above 12.5 is needed for quantitative dissociation of the adduct. After these works, small modifications have been applied and then only on specific occasions.…”

Section: Development Of the Nbp Assaymentioning

confidence: 99%

“…This approach became the most commonly used method for the estimation of alkylating agents in biological samples. ,− Other variations include gassing the sample − or changes in the solvents, ,− often aimed at avoiding the extraction step . Skibba and Collins have also proposed some modifications for the detection of antineoplastic nitrogen mustards . Additionally, after following the kinetics of the NBP alkylation reaction by a variety of alkylating agents, − Kawazoe concluded that temperature and pH must be carefully monitored because of the lability of the reactants, and a pH above 12.5 is needed for quantitative dissociation of the adduct.…”

Section: Development Of the Nbp Assaymentioning

confidence: 99%

“…Beyond discussion of its reactivity as a DNA-model, other considerations about the (dis)advantages of the NBP test must be taken into account. Apart from the ability to model the nucleophilicity of N 7 guanosine, the advantages that have encouraged the use of the NBP assay range from its simplicity (UV–vis detection), rapidness, and low costs , to its sensitivity, reproducibility, , and versatility . It has also been successfully coupled to in vitro metabolic activation systems.…”

Section: Nbp As a Dna-modelmentioning

confidence: 99%

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Potential of the NBP Method for the Study of Alkylation Mechanisms: NBP as a DNA-Model

Gómez‐Bombarelli

González‐Pérez

Calle

et al. 2012

Chem. Res. Toxicol.

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Alkylating agents are considered to be archetypal carcinogens. One suitable technique to evaluate the activity of alkylating compounds is the NBP assay. This method is based on the formation of a chromophore in the reaction between the alkylating agent and the nucleophile 4-(p-nitrobenzyl)pyridine (NBP), a trap for alkylating agents with nucleophilic characteristics similar to those of DNA bases. NBP is known to react with strong and weak alkylating agents, and much insight into such alkylation mechanisms in vivo can be gained from kinetic study of some alkylation reactions in vitro. Since 1925, the NBP assay has evolved from being a qualitative, analytical tool to becoming a useful physicochemical method that not only allows the rules of chemical reactivity that govern electrophilicity and nucleophilicity to be applied to the reaction of DNA with alkylating agents but also helps to understand some significant relationships between the structure of many alkylation substrates (including DNA) and their chemical and biological responses. Given that advances in this area have the potential to yield both fundamental and practical advances in chemistry, biology, predictive toxicology, and anticancer drug development, this review is designed to provide an overview of the evolution of the NBP method from its early inception until its recent kinetic–mechanistic approach, which allows the pros and cons of NBP as a DNA-model to be analyzed. The validity of NBP as a nucleophilicity model for DNA in general and the position of guanosine at N7 in particular are discussed.

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Section: Uses Of the Nbp Methods And Alkylation Mechanismsmentioning

confidence: 99%

Section: Development Of the Nbp Assaymentioning

confidence: 99%

Section: Development Of the Nbp Assaymentioning

confidence: 99%

Section: Nbp As a Dna-modelmentioning

confidence: 99%

See 2 more Smart Citations

Potential of the NBP Method for the Study of Alkylation Mechanisms: NBP as a DNA-Model

Gómez‐Bombarelli

González‐Pérez

Calle

et al. 2012

Chem. Res. Toxicol.

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“…Mechlorethamine hydrochloride (nitrogen mustard, HN2, NSC-762) has been used systemically as an anticancer drug since the early 1940s (Jacobson et a1 1946;Rhoads 1946). Due to its high chemical reactivity as a bifunctional alkylating agent with a wide variety of nucleophiles, including DNA, analysis of the drug in complex matrices has proved difficult (Skibba & Collins 1980). Consequently, there is only limited data on the drug's stability in solution and its pharmacokinetics and biological fate after administration (Ausman et a1 1961).…”

mentioning

confidence: 99%

The Long Term Stability of Mechlorethamine Hydrochloride (Nitrogen Mustard) Ointment Measured by HPLC

Cummings

MacLellan

Langdon

et al. 1993

Journal of Pharmacy and Pharmacology

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HPLC has been applied to determine the stability of mechlorethamine hydrochloride (nitrogen mustard) formulated as an ointment in white soft paraffin (10 mg drug, 50 g paraffin and 1 mL acetone). A new solubilization technique is described for extraction of the drug from the ointment for HPLC analysis which has an extraction efficiency of 76.1% with a coefficient of variation of 10.4%. Stored at 4 degrees C the drug content of the ointment remained stable for at least 84 days and stored at 37 degrees C the drug content remained stable for at least 40 days. In comparison aqueous solutions of mechlorethamine at the same concentration, fully degraded after 4 days. These data will aid hospital pharmacists decide on a standardized protocol for the controlled usage of the ointment which is both safe and cost-effective.

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Cross-linking by epichlorohydrin and diepoxybutane correlates with cytotoxicity and leads to apoptosis in human leukemia (HL-60) cells

Silvestri

Redstone

et al. 2018

Toxicology and Applied Pharmacology

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Modification of the 4-(p-nitrobenzyl) pyridine assay for measurement of melphalan and mechlorethamine in plasma

Cited by 7 publications

References 16 publications

Potential of the NBP Method for the Study of Alkylation Mechanisms: NBP as a DNA-Model

Potential of the NBP Method for the Study of Alkylation Mechanisms: NBP as a DNA-Model

The Long Term Stability of Mechlorethamine Hydrochloride (Nitrogen Mustard) Ointment Measured by HPLC

Cross-linking by epichlorohydrin and diepoxybutane correlates with cytotoxicity and leads to apoptosis in human leukemia (HL-60) cells

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