High-performance liquid chromatographic analysis of tamoxifen and major metabolites in human plasma

Camaggi, C. M.; Sperk, Elena; Canova, Nadia; Pannuti, F

doi:10.1016/s0378-4347(00)84393-5

Cited by 36 publications

(13 citation statements)

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“…All of these concepts require clinical confirmation and this necessitates a sensitive and specific method for analysis of TMX and related metabolites. In the present method, we adopted the principle of on-line post-HPLC Steroid receptors measured before initiation of treatment as previously described (Milano et al, 1983 column UV photocyclisation and fluorescence detection Camaggi et al, 1983). The optimal analytical conditions described herein allowed complete separation and quantification of TMX from all of the metabolites that have been reported until now in humans (Furr & Jordan, 1984).…”

Section: Discussionmentioning

confidence: 99%

“…These studies have emphasized the need for an analytical method allowing simultaneous measurement of TMX and its main metabolites not only in plasma, but also in tumoral tissue in order to examine the possible relationship between distribution of TMX and/or metabolites and tumour response. Among recently developed methods, HPLC seems the most adequate since it is both sensitive, selective and suitable for routine analysis Camaggi et al, 1983 (Kontron, Zurich, Switzerland) was equipped with 10 and 15 nm slits; voltage was set at 600 V and the gain between 0.2 and 0.5. A Hewlett-Packard 3390A integrator (Arondale, PA, USA) was used for chromatographic recording.…”

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confidence: 99%

“…A Hewlett-Packard 3390A integrator (Arondale, PA, USA) was used for chromatographic recording. The UV on-line photocyclisation system was derived from a previously described system (Camaggi et al, 1983): at the outlet of the column, a 6.5 m long Teflon capillary tube (0.35mm ID, 1.5mm OD) was arranged in 7 superposed circonvolutions (20cm diameter), with a Philips HPK 125 watt high pressure mercury lamp located in the centre. This irradiation system was enclosed in a wooden box with forced ventilation (20 x 30 x 40 cm).…”

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confidence: 99%

“…Sep pak C18 extraction (Waters Associates, Milford, MA, USA) (Camaggi et al, 1983) One ml plasma, spiked with 4 jg clomifene, was treated with 2 ml water/methanol (1:1). After vortexing and centrifugation (2000rpm, 4°C, 10min), the supernatant was filtered through the SEP PAK cartridge previously activated by the passage of 3 ml of methanol followed by 3 ml of H20.…”

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confidence: 99%

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Optimised analysis of tamoxifen and its main metabolites in the plasma and cytosol of mammary tumours

Milano¹,

Etienne²,

Frénay³

et al. 1987

Br J Cancer

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Centre Antoine Lacassagne, 36 voie Romaine, 06054 Nice Cedex, France Summary Recent biochemical and pharmacological findings concerning tamoxifen (TMX) have proven that both the unchanged drug and the main metabolites, N-desmethyltamoxifen (NDT) and 4-hydroxytamoxifen (4 OHT) are biologically active. An HPLC method based on on-line post-column UV irradiation with fluorescence detection is described. Optimized conditions allowed complete and rapid separation of TMX 40HT, NDT and two other recently reported metabolites, Y and Z. This method was applied to plasma and cytosol drug and metabolite analyses. In plasma, from the moment of initial drug administration until the steady state (after 1 month or more of continuous oral TMX treatment), the values of NDT to TMX ratios were completely reversed: 22 to 215 in mean %, P<0.01. The presence of metabolites Y and Z is significant. 40HT, hardly detectable at the first dose, was measured at the steady state with high interpatient variability. It is hypothesized that metabolite evolution with time may be due to auto-induction of drug metabolism. In cytosols, which were all obtained during continuous TMX treatment, the ratios between TMX and metabolites were comparable to those observed in plasma, but with greater interpatient variability. Metabolite Y was not detectable in cytosols. This variability was not linked to the levels of cytosolic oestradiol receptors before initiation of treatment.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Optimised analysis of tamoxifen and its main metabolites in the plasma and cytosol of mammary tumours

Milano¹,

Etienne²,

Frénay³

et al. 1987

Br J Cancer

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“…In contrast, a method of post column fluorescence activation [91] or preliminary purification from interfering substance using a Sep-Pack C18 cartridge (Waters Association, Milford MA) [92] with internal standardization considerably improved accuracy. The detection of tamoxifen metabolites in serum was further improved by Lien and coworkers [93] and recently by Lee and coworkers [94] who adapted the methods [95,96] developed to perform "on line" extraction and post column cyclization.…”

Section: Clinical Pharmacologymentioning

confidence: 99%

New insights into the metabolism of tamoxifen and its role in the treatment and prevention of breast cancer

2007

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The metabolism of tamoxifen is being redefined in the light of several important pharmacological observations. Recent studies have identified 4-hydroxy N-desmethyl tamoxifen (endoxifen) as an important metabolite of tamoxifen necessary for antitumor actions. The metabolite is formed through the enzymatic product of CYP2D6 which also interacts with specific selective serotonin reuptake inhibitors (SSRIs) used to prevent the hot flashes observed in up to 45% of patients taking tamoxifen. Additionally, the finding that enzyme variants of CYP2D6 do not promote the metabolism of tamoxifen to endoxifen means that significant numbers of women might not receive optimal benefit from tamoxifen treatment. Clearly these are particularly important issues not only for breast cancer treatment but also for selecting premenopausal women, at high risk for breast cancer, as candidates for chemoprevention using tamoxifen.

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Biomonitoring of urinary tamoxifen and its metabolites from breast cancer patients using nonaqueous capillary electrophoresis with electrospray mass spectrometry

Carter

Mackey

et al. 2001

Electrophoresis

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Tamoxifen is an antiestrogen drug used to treat breast cancer. We have extracted tamoxifen and several of its metabolites from urine of patients with both metastatic (stage IV) and locally confined (stages I, II, and III) breast cancer. Analysis of these metabolites was performed by nonaqueous capillary electrophoresis with electrospray-mass spectrometry. Peak heights from extracted ion current electropherograms of the metabolites were used to establish a metabolic profile for each patient. We demonstrate substantial variation among patient profiles, statistically significant differences in the amount of urinary tamoxifen N-oxide found in stages I, II, and III compared to stage IV breast cancer patients, and statistically significant differences in the amount of 3,4-dihydroxytamoxifen found in progressors compared to nonprogressors with metastatic (stage IV) cancer.

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High-performance liquid chromatographic analysis of tamoxifen and major metabolites in human plasma

Cited by 36 publications

References 7 publications

Optimised analysis of tamoxifen and its main metabolites in the plasma and cytosol of mammary tumours

Optimised analysis of tamoxifen and its main metabolites in the plasma and cytosol of mammary tumours

New insights into the metabolism of tamoxifen and its role in the treatment and prevention of breast cancer

Biomonitoring of urinary tamoxifen and its metabolites from breast cancer patients using nonaqueous capillary electrophoresis with electrospray mass spectrometry

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