Determination of cyclophosphamide in whole blood and plasma by reversed-phase high-performance liquid chromatography

Rustum, Abu M.; Hoffman, Norman E.

doi:10.1016/0378-4347(87)80445-0

Cited by 26 publications

(11 citation statements)

References 8 publications

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“…Cyclophosphamide has been measured by gas chromatography (GC) with derivatisation, GC-mass spectrometry (MS) and bioassay (EI-Yazigi & Martin 1986;Juma et al 1979;Sladek et al 1984). More recent methods have used high performance liquid chromatography (HPLC), but these are difficult because of the low UV detection wavelength (200nm) and the extraction procedures necessary (Burton & James 1989;Hardy et al 1984;Rustum et al 1987).…”

Section: Discussionmentioning

confidence: 99%

Clinical Pharmacokinetics of Cyclophosphamide

Moore

1991

Clinical Pharmacokinetics

255

131

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Cyclophosphamide has been in clinical use for the treatment of malignant disease for over 30 years. It remains one of the most useful anticancer agents, and is also widely used for its immunosuppressive properties. Cyclophosphamide is inactive until it undergoes hepatic transformation to form 4-hydroxycyclophosphamide, which then breaks down to form the ultimate alkylating agent, phosphoramide mustard. Sensitive and specific methods are now available for the measurement of cyclophosphamide, its metabolites and its stereoisomers in plasma and urine. The pharmacokinetics of cyclophosphamide have been understood for many years; those of the cytotoxic metabolites have been described more recently. The pharmacokinetics are not significantly altered in the presence of hepatic or renal insufficiency. As activity resides exclusively in the metabolites, whose pharmacokinetics are not predicted by those of the parent compound, correlations between cyclophosphamide pharmacokinetics and pharmacodynamics have not been demonstrated. Cyclophosphamide is used in doses that range from 1.5 to 60 mg/kg/day. A steep dose-response curve exists, and reductions in dose can lead to unfavourable outcomes. Myelosuppression is the dose-limiting toxicity, although in the setting of bone marrow transplantation, escalation beyond that dosage range is limited by cardiac toxicity. Longer term complications of cyclophosphamide therapy include infertility and an increased incidence of second malignancies. Cellular sensitivity to cyclophosphamide is a function of cellular thiol concentration, metabolism by aldehyde dehydrogenases to form inactive metabolites, and the ability of DNA to repair alkylated nucleotides. Whether alteration of these cellular functions will lead to further improvements in clinical outcomes is an area of active investigation.

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Section: Discussionmentioning

confidence: 99%

Clinical Pharmacokinetics of Cyclophosphamide

Moore

1991

Clinical Pharmacokinetics

255

131

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“…Our preliminary conditions for the HPLC method were based on several previous studies, which used a mobile phase comprised of 20% acetonitrile and 80% phosphate buffer 17, 18. We found that with our initial assay conditions, substances in Ora-Plus caused peaks that overlapped with the cyclophosphamide and ifosfamide peaks.…”

Section: Discussionmentioning

confidence: 99%

“…Chromatographic data were analyzed using Shimadzu ClassVP Integrating Software v. 7.3. Our preliminary conditions were based on previously reported methods 17, 18. All chromatographic separations were obtained using a Phenomenex® Luna, 5µm, C18, 100Å, 125 × 4 mm column (Torrance, CA, USA) with a Phenomenex® Security Guard, C18, 4 × 2.0 mm guard column.…”

Section: Methodsmentioning

confidence: 99%

Stability of Cyclophosphamide in Extemporaneous Oral Suspensions

et al. 2010

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“…There are notable methods available, such as gas chromatography with mass detector (GC-MS) [6], high performance liquid chromatography (HPLC) [7][8][9][10][11][12], and UVspectrophotometric methods [1, 13 and 14]. Recently, Liquid chromatography with mass detector (LC-MS) methods [15][16][17][18][19][20] and UPLC-MS/MS methods [21,22], have been also been used to measure the CP in formulations and biological samples.…”

Section: Introductionmentioning

confidence: 99%

Application of Charge Transfer Reactions for the Quantitative Spectrophotometric Determination of Cyclophosphamide in Pure and Pharmaceutical Formulation

Siddappa

Hanamshetty²

2015

CPA

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The present investigation describes two simple, sensitive and validated spectrophotometric methods for the determination of Cyclophosphamide (CP) in pure and formulated forms. The methods are mainly based on the formation of charge transfer (CT) complex, with the reagents 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) (Method A) and p-Chloranilic acid (PCA) (Method B), hence a stable, 1:1 stoichiometric complex was obtained, which shows orangeyellow and pink colors, respectively. The produced chromogens optical densities were measured at 352 and 522 nm, respectively. The Beer's law was tested in the range of 2-16 and 5-50 µg mL -1 . The optical characteristics such as molar absorptivity (ɛ), and Sandell's sensitivity values were calculated. Other analytical parameters like, Limit of Detection (LOD), Limit of Quantification (LOQ), accuracy and precisions were evaluated. The proposed methods were successfully applied for the determination of the CP in tablet formulation with higher accuracy, better recoveries and less than 2% relative standard deviation.

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Determination of cyclophosphamide in whole blood and plasma by reversed-phase high-performance liquid chromatography

Cited by 26 publications

References 8 publications

Clinical Pharmacokinetics of Cyclophosphamide

Clinical Pharmacokinetics of Cyclophosphamide

Stability of Cyclophosphamide in Extemporaneous Oral Suspensions

Application of Charge Transfer Reactions for the Quantitative Spectrophotometric Determination of Cyclophosphamide in Pure and Pharmaceutical Formulation

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