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Paraskevas D Tzanavaras - One of the best experts on this subject based on the ideXlab platform.

  • Assay of the synthetic estrogen Fosfestrol in pharmaceutical formulations using capillary electrophoresis.
    Journal of pharmaceutical and biomedical analysis, 2005
    Co-Authors: Demetrius G Themelis, Anastasios V Trellopoulos, Paraskevas D Tzanavaras, Bo Karlberg
    Abstract:

    This study reports--for the first time--a capillary electrophoretic method for the determination of Fosfestrol, a synthetic estrogen used in the treatment of metastatic prostate cancer. The effects of the carrier ion concentration, injected volume and applied voltage were studied and optimized. A 10 mM sodium tetraborate solution was selected as the carrier electrolyte solution, while the sample was injected hydrodynamically by applying a 20 mmHg vacuum for 1 s. The driving voltage was 30 kV and the absorbance of the analyte (peak height) was monitored at 240 nm. Under the above-mentioned conditions, the migration time of Fosfestrol was 6.6 min. Linearity was achieved in the analyte range 3-150 mgL(-1) with the detection limit being 1 mgL(-1). The proposed method is adequately precise (s(r)=2.8% at 100 mgL(-1) Fosfestrol, n=10) without the use of an internal standard and was applied to the determination of Fosfestrol in a pharmaceutical formulation. The results obtained by the proposed method were in good agreement with those derived from the USP reference method.

  • Flow injection spectrophotometric determination of Fosfestrol, following on-line thermal induced digestion and using an orthophosphate calibration graph.
    Talanta, 2003
    Co-Authors: Paraskevas D Tzanavaras, Demetrius G Themelis
    Abstract:

    A novel flow injection (FI) system for the spectrophotometric determination of diethyl stilbestrol diphosphate (Fosfestrol) in pharmaceutical formulations is described. On-line thermal induced digestion of the analyte by peroxodisulfate ion was performed and the orthophosphate ion generated was determined spectrophotometrically (lambda(max)=690 nm) using a molybdenum blue based FI approach. As the achieved conversion of the analyte was quantitative, an orthophosphate calibration graph can be used for its determination as well. The chemical and FI variables affecting the digestion were investigated. A linear calibration graph was obtained in the range 5.0x10(-7)-1.0x10(-4) mol l(-1) Fosfestrol. The relative standard deviation was very good (s(r)=0.8% at 5.0x10(-5) mol l(-1) Fosfestrol, n=12) and the 3sigma detection limit was 2.5x10(-7) mol l(-1). The sampling rate was 60 injections h(-1). The average accuracies for the determination of the analyte in a pharmaceutical formulation evaluated by comparison of the results with those obtained by the supplier (Asta Medica) and the method recommended by the US Pharmacopoeia were also very good (e(r) of +0.8 and -0.3%, respectively). Average recoveries of known amounts of the analyte ranging between 97.9 and 100.8% were also obtained.

  • rapid spectrophotometric determination of Fosfestrol following on line hydrolysis by alkaline phosphatase using flow injection and chasing zones
    Analytica Chimica Acta, 2002
    Co-Authors: Paraskevas D Tzanavaras, Demetrius G Themelis, Bo Karlberg
    Abstract:

    Abstract A new flow injection (FI) method is reported for the spectrophotometric determination of Fosfestrol (diethyl-stilbestrol (DES) diphosphate) in pharmaceutical formulations. The proposed method is based on the on-line hydrolysis of the analyte by alkaline phosphatase (Al-Pase) using a “chasing zones” FI manifold. The orthophosphate ions, thus, generated are determined spectrophotometrically (λmax=690 nm) using the molybdenum blue approach. The chemical and FI variables affecting the enzymatic reaction were investigated. The proposed method is very precise (sr=1.1% at 1×10−4 mol l−1 Fosfestrol, n=12), fast (allowing up to 40 samples h−1 to be analyzed) and has a determination range of 2×10−5 to 2×10−4 mol l−1, with a satisfactory 3σ detection limit of 5×10−6 mol l−1. The method was shown to provide accurate determinations of the Fosfestrol concentration in a pharmaceutical formulation, giving relative errors, er, of +0.6 and −0.5% compared to the value stated by the supplier (Asta Medica Inc.) and the concentration derived using a method recommended by the United States Pharmacopoeia XXI, respectively. In addition, the average recoveries of known amounts of the analyte ranged between 99.2 and 101.2%.

Bo Karlberg - One of the best experts on this subject based on the ideXlab platform.

  • Assay of the synthetic estrogen Fosfestrol in pharmaceutical formulations using capillary electrophoresis.
    Journal of pharmaceutical and biomedical analysis, 2005
    Co-Authors: Demetrius G Themelis, Anastasios V Trellopoulos, Paraskevas D Tzanavaras, Bo Karlberg
    Abstract:

    This study reports--for the first time--a capillary electrophoretic method for the determination of Fosfestrol, a synthetic estrogen used in the treatment of metastatic prostate cancer. The effects of the carrier ion concentration, injected volume and applied voltage were studied and optimized. A 10 mM sodium tetraborate solution was selected as the carrier electrolyte solution, while the sample was injected hydrodynamically by applying a 20 mmHg vacuum for 1 s. The driving voltage was 30 kV and the absorbance of the analyte (peak height) was monitored at 240 nm. Under the above-mentioned conditions, the migration time of Fosfestrol was 6.6 min. Linearity was achieved in the analyte range 3-150 mgL(-1) with the detection limit being 1 mgL(-1). The proposed method is adequately precise (s(r)=2.8% at 100 mgL(-1) Fosfestrol, n=10) without the use of an internal standard and was applied to the determination of Fosfestrol in a pharmaceutical formulation. The results obtained by the proposed method were in good agreement with those derived from the USP reference method.

  • rapid spectrophotometric determination of Fosfestrol following on line hydrolysis by alkaline phosphatase using flow injection and chasing zones
    Analytica Chimica Acta, 2002
    Co-Authors: Paraskevas D Tzanavaras, Demetrius G Themelis, Bo Karlberg
    Abstract:

    Abstract A new flow injection (FI) method is reported for the spectrophotometric determination of Fosfestrol (diethyl-stilbestrol (DES) diphosphate) in pharmaceutical formulations. The proposed method is based on the on-line hydrolysis of the analyte by alkaline phosphatase (Al-Pase) using a “chasing zones” FI manifold. The orthophosphate ions, thus, generated are determined spectrophotometrically (λmax=690 nm) using the molybdenum blue approach. The chemical and FI variables affecting the enzymatic reaction were investigated. The proposed method is very precise (sr=1.1% at 1×10−4 mol l−1 Fosfestrol, n=12), fast (allowing up to 40 samples h−1 to be analyzed) and has a determination range of 2×10−5 to 2×10−4 mol l−1, with a satisfactory 3σ detection limit of 5×10−6 mol l−1. The method was shown to provide accurate determinations of the Fosfestrol concentration in a pharmaceutical formulation, giving relative errors, er, of +0.6 and −0.5% compared to the value stated by the supplier (Asta Medica Inc.) and the concentration derived using a method recommended by the United States Pharmacopoeia XXI, respectively. In addition, the average recoveries of known amounts of the analyte ranged between 99.2 and 101.2%.

Demetrius G Themelis - One of the best experts on this subject based on the ideXlab platform.

  • Flow injection spectrophotometric determination of Fosfestrol, following on-line thermal induced digestion and using an orthophosphate calibration graph.
    Talanta, 2003
    Co-Authors: Paraskevas D Tzanavaras, Demetrius G Themelis
    Abstract:

    A novel flow injection (FI) system for the spectrophotometric determination of diethyl stilbestrol diphosphate (Fosfestrol) in pharmaceutical formulations is described. On-line thermal induced digestion of the analyte by peroxodisulfate ion was performed and the orthophosphate ion generated was determined spectrophotometrically (lambda(max)=690 nm) using a molybdenum blue based FI approach. As the achieved conversion of the analyte was quantitative, an orthophosphate calibration graph can be used for its determination as well. The chemical and FI variables affecting the digestion were investigated. A linear calibration graph was obtained in the range 5.0x10(-7)-1.0x10(-4) mol l(-1) Fosfestrol. The relative standard deviation was very good (s(r)=0.8% at 5.0x10(-5) mol l(-1) Fosfestrol, n=12) and the 3sigma detection limit was 2.5x10(-7) mol l(-1). The sampling rate was 60 injections h(-1). The average accuracies for the determination of the analyte in a pharmaceutical formulation evaluated by comparison of the results with those obtained by the supplier (Asta Medica) and the method recommended by the US Pharmacopoeia were also very good (e(r) of +0.8 and -0.3%, respectively). Average recoveries of known amounts of the analyte ranging between 97.9 and 100.8% were also obtained.

  • rapid spectrophotometric determination of Fosfestrol following on line hydrolysis by alkaline phosphatase using flow injection and chasing zones
    Analytica Chimica Acta, 2002
    Co-Authors: Paraskevas D Tzanavaras, Demetrius G Themelis, Bo Karlberg
    Abstract:

    Abstract A new flow injection (FI) method is reported for the spectrophotometric determination of Fosfestrol (diethyl-stilbestrol (DES) diphosphate) in pharmaceutical formulations. The proposed method is based on the on-line hydrolysis of the analyte by alkaline phosphatase (Al-Pase) using a “chasing zones” FI manifold. The orthophosphate ions, thus, generated are determined spectrophotometrically (λmax=690 nm) using the molybdenum blue approach. The chemical and FI variables affecting the enzymatic reaction were investigated. The proposed method is very precise (sr=1.1% at 1×10−4 mol l−1 Fosfestrol, n=12), fast (allowing up to 40 samples h−1 to be analyzed) and has a determination range of 2×10−5 to 2×10−4 mol l−1, with a satisfactory 3σ detection limit of 5×10−6 mol l−1. The method was shown to provide accurate determinations of the Fosfestrol concentration in a pharmaceutical formulation, giving relative errors, er, of +0.6 and −0.5% compared to the value stated by the supplier (Asta Medica Inc.) and the concentration derived using a method recommended by the United States Pharmacopoeia XXI, respectively. In addition, the average recoveries of known amounts of the analyte ranged between 99.2 and 101.2%.

J. H. Williams - One of the best experts on this subject based on the ideXlab platform.

  • High dose intravenous oestrogen (Fosfestrol) in the treatment of symptomatic, metastatic, hormone-refractory carcinoma of the prostate
    International Urology and Nephrology, 1998
    Co-Authors: M. Ahmed, S. Choksy, C. P. Chilton, K. W. Munson, J. H. Williams
    Abstract:

    Objective High dose intravenous stilboestrol has a direct cytotoxic effect on prostatic carcinoma cells. The purpose of this study was to assess subjective and objective responses in a select group of patients with metastatic, hormonerefractory carcinoma of the prostate with severe generalized bone pain in association with symptoms of advanced local disease. Patients and methods Seventeen patients with metastatic carcinoma of the prostate, who had relapsed following a good initial response to androgen ablation, were treated as inpatients with once daily intravenous injection of 1104 mg diethylstilboestrol diphosphate (Honvan^™, Asta Medica, Cambridge, UK) for 7 days. The hormone-refractory status was confirmed by castrate serum testosterone levels. All the patients had failed to respond to second-line hormone manipulation and had progressive disease. All the patients had generalized bone pain, 11 also had symptoms of bladder outlet obstruction, 3 had recurrent haematuria and 3 had both. The mean age was 74 years (range 59–83), mean time to chemical relapse (rising PSA) was 29 months (range 1–70), and mean time to clinical relapse was 37 months (range 6–98). The WHO pain score, performance status score, and a patient-specific quality of life (daily living activity) were used as the subjective measures and the serum PSA as an objective marker. All the parameters were recorded before, during and up to three months after treatment. Results Two patients had a transient relief of bone pain with the pain score reducing by two points. Overall, the pain and performance scores and the local symptoms did not improve. The PSA level continued to rise in all patients. Despite parenteral pre-medication with pethidine and cyclizine, all the patients suffered nausea and pain following the injection. One patient died on the fifth day of treatment from a myocardial infarction and 4 developed deep vein thrombosis. All the patients required further symptom control measures. Conclusion High dose intravenous stilboestrol causes considerable morbidity without any objective or subjective response in the treatment of patients with symptomatic, hormone-refractory metastatic carcinoma of the prostate.

  • High dose intravenous oestrogen (Fosfestrol) in the treatment of symptomatic, metastatic, hormone-refractory carcinoma of the prostate.
    International urology and nephrology, 1998
    Co-Authors: M. Ahmed, S. Choksy, C. P. Chilton, K. W. Munson, J. H. Williams
    Abstract:

    Objective High dose intravenous stilboestrol has a direct cytotoxic effect on prostatic carcinoma cells. The purpose of this study was to assess subjective and objective responses in a select group of patients with metastatic, hormonerefractory carcinoma of the prostate with severe generalized bone pain in association with symptoms of advanced local disease.

Jamsheer J Talati - One of the best experts on this subject based on the ideXlab platform.

  • Original Articles Role of Estrogens in the Secondary Hormonal Manipulation of Hormone Refractory Prostate Cancer
    2015
    Co-Authors: Khurram Siddiqui, Farhat Abbas, Syed Raziuddin Biyabani, M. H. Ather, Jamsheer J Talati
    Abstract:

    Objective: To evaluate the role of Estrogens (Honvan) in the secondary hormonal manipulation of patients with hormone refractory prostate cancer (HRCP). Methods: Twelve patients diagnosed as hormone refractory prostate cancer received intravenous estrogens for six days (Fosfestrol, a synthetic phosphorylated estrogen derivative), followed by a maintenance oral dose of 120 mg thrice daily as second line hormonal treatment. During the treatment they were given deep venous thrombo-sis prophylaxis. Their stage at initial presentation, primary treatment, mode of androgen ablation, prostate spe-cific antigen (PSA) level, duration of remission prior of HRPC status, PSA doubling time before and after estro-gen treatment were recorded. The morbidity and mortality of the treatment was also recorded. A drop in PSA of> 50 % was classified as major responder. The drop of < 50 % was defined as minor responders. Treatment fail-ure was defined as a rise in PSA> the level prior to the start of treatment. Results: The mean age at diagnosis of prostate cancer was 66.6 + 5.4 years (range 57-73). At the time of ini-tial diagnosis only 3 patients (25%) had localized disease and 9 (75%) had metastatic prostate cancer. Six patients each opted for surgical or medical castration (LHRH analogs) as the mode of androgen ablation. The mean initial PSA at diagnosis was 340 + 728.1 ng/ml (range 4.1-2375, Median 94). After development of HRPC, six patients (50%) had major response, four (33%) had minor response to estrogen administration. Two patients (17%) did not respond to estrogens. The mean PSA before receiving Fosfestrol was 60.5 + 82 ng/ml (range 0.013-246). The PSA (nadir) after treatment was 24.3 + 33.2 ng/ml (range 0.9-81.3). One patient developed gynaecomastia and one had congestive cardiac failure. Two patients died of non cancer related deaths and one patient died of cancer related death. Conclusion: Synthetic estrogens are well tolerated, in-expensive agents and could be considered for palliative use against hormone resistant prostate cancer (JPMA 54:445;2004)

  • Role of estrogens in the secondary hormonal manipulation of hormone refractory prostate cancer.
    JPMA. The Journal of the Pakistan Medical Association, 2004
    Co-Authors: Khurram Siddiqui, Farhat Abbas, Syed Raziuddin Biyabani, Jamsheer J Talati
    Abstract:

    Objective: To evaluate the role of Estrogens (Honvan) in the secondary hormonal manipulation of patients with hormone refractory prostate cancer (HRCP). Methods: Twelve patients diagnosed as hormone refractory prostate cancer received intravenous estrogens for six days (Fosfestrol, a synthetic phosphorylated estrogen derivative), followed by a maintenance oral dose of 120 mg thrice daily as second line hormonal treatment. During the treatment they were given deep venous thrombosis prophylaxis. Their stage at initial presentation, primary treatment, mode of androgen ablation, prostate specific antigen (PSA) level, duration of remission prior of HRPC status, PSA doubling time before and after estrogen treatment were recorded. The morbidity and mortality of the treatment was also recorded. A drop in PSA of > 50% was classified as major responder. The drop of the level prior to the start of treatment. Results: The mean age at diagnosis of prostate cancer was 66.6 + 5.4 years (range 57-73). At the time of initial diagnosis only 3 patients (25%) had localized disease and 9 (75%) had metastatic prostate cancer. Six patients each opted for surgical or medical castration (LHRH analogs) as the mode of androgen ablation. The mean initial PSA at diagnosis was 340 + 728.1 ng/ml (range 4.1-2375, Median 94). After development of HRPC, six patients (50%) had major response, four (33%) had minor response to estrogen administration. Two patients (17%) did not respond to estrogens. The mean PSA before receiving Fosfestrol was 60.5 + 82 ng/ml (range 0.013-246). The PSA (nadir) after treatment was 24.3 + 33.2 ng/ml (range 0.9-81.3). One patient developed gynaecomastia and one had congestive cardiac failure. Two patients died of non cancer related deaths and one patient died of cancer related death. Conclusion: Synthetic estrogens are well tolerated, in-expensive agents and could be considered for palliative use against hormone resistant prostate cancer (JPMA 54:445;2004).

  • Original Articles Role of Estrogens in the Secondary Hormonal Manipulation of Hormone Refractory Prostate Cancer
    2004
    Co-Authors: Khurram M. Siddiqui, Khurram Siddiqui, Farhat Abbas, Syed Raziuddin Biyabani, Jamsheer J Talati, M. H. Ather, Hammad M Ather
    Abstract:

    Objective: To evaluate the role of Estrogens (Honvan) in the secondary hormonal manipulation of patients with hormone refractory prostate cancer (HRCP). Methods: Twelve patients diagnosed as hormone refractory prostate cancer received intravenous estrogens for six days (Fosfestrol, a synthetic phosphorylated estrogen derivative), followed by a maintenance oral dose of 120 mg thrice daily as second line hormonal treatment. During the treatment they were given deep venous thrombo-sis prophylaxis. Their stage at initial presentation, primary treatment, mode of androgen ablation, prostate spe-cific antigen (PSA) level, duration of remission prior of HRPC status, PSA doubling time before and after estro-gen treatment were recorded. The morbidity and mortality of the treatment was also recorded. A drop in PSA of> 50 % was classified as major responder. The drop of < 50 % was defined as minor responders. Treatment fail-ure was defined as a rise in PSA> the level prior to the start of treatment. Results: The mean age at diagnosis of prostate cancer was 66.6 + 5.4 years (range 57-73). At the time of ini-tial diagnosis only 3 patients (25%) had localized disease and 9 (75%) had metastatic prostate cancer. Si