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Androgen glucuronides analysis by liquid chromatography tandem-mass spectrometry: Could it raise new perspectives in the diagnostic field of hormone-dependent malignancies?
18 October 2013,
10:35:40
Publication date: 1 December
2013
Source:Journal of Chromatography B, Volume 940
Author(s): Eleni Kalogera , Constantinos Pistos , Xeni Provatopoulou , Sotirios Athanaselis , Chara Spiliopoulou , Antonia Gounaris
Breast and prostate constitute organs of intense steroidogenic activity. Clinical and epidemiologic data provide strong evidence on the influence of androgens and estrogens on the risk of typical hormone-dependent malignancies, like breast and prostate cancer. Recent studies have focused on the role of androgen metabolites in regulating androgen concentrations in hormone-sensitive tissues. Steroid glucuronidation has been suggested to have a prominent role in controlling the levels and the biological activity of unconjugated androgens. It is well-established that serum levels of androgen glucuronides reflect androgen metabolism in androgen-sensitive tissues. Quantitative analysis of androgen metabolites in blood specimens is the only minimally invasive approach permitting an accurate estimate of the total pool of androgens. During the past years, androgen glucuronides analysis most often involved radioimmunoassays (RIA) or direct immunoassays, both methods bearing serious limitations. However, recent impressive technical advances in mass spectrometry, and particularly in high performance liquid chromatography coupled with mass spectrometry (LC–MS/MS), have overcome these drawbacks enabling the simultaneous, quantitative analysis of multiple steroids even at low concentrations. Blood androgen profiling by LC–MS/MS, a robust and reliable technique of high selectivity, sensitivity, specificity, precision and accuracy emerges as a promising new approach in the study of human pathology. The present review offers a contemporary insight in androgen glucuronides profiling through the application of LC–MS/MS, highlighting new perspectives in the study of steroids and their implication in hormone-dependent malignancies.
Source:Journal of Chromatography B, Volume 940
Author(s): Eleni Kalogera , Constantinos Pistos , Xeni Provatopoulou , Sotirios Athanaselis , Chara Spiliopoulou , Antonia Gounaris
Breast and prostate constitute organs of intense steroidogenic activity. Clinical and epidemiologic data provide strong evidence on the influence of androgens and estrogens on the risk of typical hormone-dependent malignancies, like breast and prostate cancer. Recent studies have focused on the role of androgen metabolites in regulating androgen concentrations in hormone-sensitive tissues. Steroid glucuronidation has been suggested to have a prominent role in controlling the levels and the biological activity of unconjugated androgens. It is well-established that serum levels of androgen glucuronides reflect androgen metabolism in androgen-sensitive tissues. Quantitative analysis of androgen metabolites in blood specimens is the only minimally invasive approach permitting an accurate estimate of the total pool of androgens. During the past years, androgen glucuronides analysis most often involved radioimmunoassays (RIA) or direct immunoassays, both methods bearing serious limitations. However, recent impressive technical advances in mass spectrometry, and particularly in high performance liquid chromatography coupled with mass spectrometry (LC–MS/MS), have overcome these drawbacks enabling the simultaneous, quantitative analysis of multiple steroids even at low concentrations. Blood androgen profiling by LC–MS/MS, a robust and reliable technique of high selectivity, sensitivity, specificity, precision and accuracy emerges as a promising new approach in the study of human pathology. The present review offers a contemporary insight in androgen glucuronides profiling through the application of LC–MS/MS, highlighting new perspectives in the study of steroids and their implication in hormone-dependent malignancies.
(S)-1-(4-Dimethylaminophenylcarbonyl)-3-aminopyrrolidine: A derivatization reagent for enantiomeric separation and sensitive detection of chiral carboxylic acids by LC/ESI-MS/MS
18 October 2013,
10:35:40
Publication date: 1 December
2013
Source:Journal of Chromatography B, Volume 940
Author(s): Shoujiro Ogawa , Hiroaki Tadokoro , Maho Sato , Takehisa Hanawa , Tatsuya Higashi
A novel derivatization reagent, (S)-1-(4-dimethylaminophenylcarbonyl)-3-aminopyrrolidine (1-DAPAP), was developed for increasing the detection sensitivity and enantiomeric separation of chiral carboxylic acids by liquid chromatography/electrospray ionization–tandem mass spectrometry (LC/ESI-MS/MS). 1-DAPAP reacted with carboxylic acids at room temperature within 5min in the presence of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride. The epimerization (racemization) during the derivatization reaction was negligible. The resulting derivatives were highly responsive during the ESI-MS operating in the positive-ion mode and gave a characteristic product ion during the MS/MS, which enabled the sensitive detection using selected reaction monitoring; the detection responses of the 1-DAPAP-derivatives were increased by 10–1100-fold over the intact carboxylic acids and the limits of detection ranged from 0.97 and 5.2fmol on the column. The 1-DAPAP-derivatization was also effective for the enantiomeric separation of chiral carboxylic acids; the resolution values were 1.2–4.3 for the evaluated carboxylic acids. The derivatization procedure was successfully applied to biological sample analyses; the derivatization followed by LC/ESI-MS/MS enabled the separation and detection of trace amounts of ibuprofen and naproxen in human saliva with a simple pretreatment and small sample volume.
Source:Journal of Chromatography B, Volume 940
Author(s): Shoujiro Ogawa , Hiroaki Tadokoro , Maho Sato , Takehisa Hanawa , Tatsuya Higashi
A novel derivatization reagent, (S)-1-(4-dimethylaminophenylcarbonyl)-3-aminopyrrolidine (1-DAPAP), was developed for increasing the detection sensitivity and enantiomeric separation of chiral carboxylic acids by liquid chromatography/electrospray ionization–tandem mass spectrometry (LC/ESI-MS/MS). 1-DAPAP reacted with carboxylic acids at room temperature within 5min in the presence of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride. The epimerization (racemization) during the derivatization reaction was negligible. The resulting derivatives were highly responsive during the ESI-MS operating in the positive-ion mode and gave a characteristic product ion during the MS/MS, which enabled the sensitive detection using selected reaction monitoring; the detection responses of the 1-DAPAP-derivatives were increased by 10–1100-fold over the intact carboxylic acids and the limits of detection ranged from 0.97 and 5.2fmol on the column. The 1-DAPAP-derivatization was also effective for the enantiomeric separation of chiral carboxylic acids; the resolution values were 1.2–4.3 for the evaluated carboxylic acids. The derivatization procedure was successfully applied to biological sample analyses; the derivatization followed by LC/ESI-MS/MS enabled the separation and detection of trace amounts of ibuprofen and naproxen in human saliva with a simple pretreatment and small sample volume.
Determination of stilbenes and resorcylic acid lactones in bovine, porcine and poultry muscle tissue by liquid chromatography–negative ion electrospray mass spectrometry and QuEChERS for sample preparation
18 October 2013,
10:35:40
Publication date: 1 December
2013
Source:Journal of Chromatography B, Volume 940
Author(s): Barbara Wozniak , Iwona Matraszek Zuchowska , Jan Zmudzki
Liquid chromatography tandem mass spectrometry method was developed and validated to confirm of resorcylic acid lactones: zeranol, taleranol, zearalanone, zearalenone, α and β-zearalenol and stilbenes in muscle tissue. The compounds were analyzed by LC–MS/MS QTrap 5500 apparatus in negative ionization mode. Chromatographic separation on Poroshell 120-EC C18 (150mm×2.1mm, 2.7μm) column was achieved at 45°C using isocratic elution of mobile phase – methanol/water (65:35, v/v). For the treatment of tissue samples prior to analysis, QuEChERS method was applied based on the extraction of analytes from muscle samples with ethyl acetate, separation of the aqueous and organic phases with application of magnesium sulphate and sodium acetate, the purification of the extract obtained by dispersive SPE with the use of sorbent C18, PSA and magnesium sulphate. The method was validated in accordance with the Commission Decision 2002/657/EC. Good recoveries were obtained (from 83% to 115%) as well as acceptable within-lab reproducibility (<22%). The values of the decision limit CCα and the detection capability CCβ for individual compounds are found to be below the recommended concentration set at 1μgkg−1 and not exceed 0.23μgkg−1 and 0.39μgkg−1, respectively. The elaborated method meets the criteria for confirmatory methods and is used in the official control of hormones.
Source:Journal of Chromatography B, Volume 940
Author(s): Barbara Wozniak , Iwona Matraszek Zuchowska , Jan Zmudzki
Liquid chromatography tandem mass spectrometry method was developed and validated to confirm of resorcylic acid lactones: zeranol, taleranol, zearalanone, zearalenone, α and β-zearalenol and stilbenes in muscle tissue. The compounds were analyzed by LC–MS/MS QTrap 5500 apparatus in negative ionization mode. Chromatographic separation on Poroshell 120-EC C18 (150mm×2.1mm, 2.7μm) column was achieved at 45°C using isocratic elution of mobile phase – methanol/water (65:35, v/v). For the treatment of tissue samples prior to analysis, QuEChERS method was applied based on the extraction of analytes from muscle samples with ethyl acetate, separation of the aqueous and organic phases with application of magnesium sulphate and sodium acetate, the purification of the extract obtained by dispersive SPE with the use of sorbent C18, PSA and magnesium sulphate. The method was validated in accordance with the Commission Decision 2002/657/EC. Good recoveries were obtained (from 83% to 115%) as well as acceptable within-lab reproducibility (<22%). The values of the decision limit CCα and the detection capability CCβ for individual compounds are found to be below the recommended concentration set at 1μgkg−1 and not exceed 0.23μgkg−1 and 0.39μgkg−1, respectively. The elaborated method meets the criteria for confirmatory methods and is used in the official control of hormones.
Development of a high performance liquid chromatography method for quantification of isomers β-caryophyllene and α-humulene in copaiba oleoresin using the Box-Behnken design
18 October 2013,
10:35:40
Publication date: 1 December
2013
Source:Journal of Chromatography B, Volume 940
Author(s): Vinícius Raphael de Almeida Borges , Ana Ferreira Ribeiro , Carina de Souza Anselmo , Lúcio Mendes Cabral , Valéria Pereira de Sousa
The sesquiterpene isomers, β-Cariofileno (CAR) and α-Humuleno (HUM) are the primary constituents of the copaiba oleoresin species. These natural products are primarily used by the Amazonian population and marketed as phytotherapies and cosmetics. The aim of this study was to develop and validate a method that simultaneously assays the isomers present in copaiba oleoresins by high performance liquid chromatography using the Box-Behnken design. After preliminary studies, the reverse phase chromatographic system was selected using a cyano column and a mobile phase consisting of acetonitrile and phosphate buffer. The Box-Behnken design was applied at three levels and with four independent variables: flow rate (X 1), gradient slope time (X 2), proportion of organic compounds at the end of the gradient (X 3) and at the beginning of the gradient (X 4). Also, the responses of the dependent variables: CAR retention time (Y 1) and the resolution between the CAR and HUM peaks (Y 2) was assessed. The mathematical model obtained from the regression results was satisfactory (R 2 >0.98, n =27) and showed a quadratic relationship where the effects of interactions between the variables, was observed by response surface graphs. The simultaneous optimization method was used to establish the best compromise of the resolution between the CAR and HUM isomers while adjusting the retention time of CAR. This method was successfully optimized by BBD obtaining chromatographic peaks with good symmetry, resolution and separation efficiency. The validation of the developed method confirmed its specificity, precision, accuracy and linearity in the range of 5.0–11.0 and 0.4–1.0μg/mL for CAR and HUM, respectively, and is considered suitable for routine applications which assure quality control.
Source:Journal of Chromatography B, Volume 940
Author(s): Vinícius Raphael de Almeida Borges , Ana Ferreira Ribeiro , Carina de Souza Anselmo , Lúcio Mendes Cabral , Valéria Pereira de Sousa
The sesquiterpene isomers, β-Cariofileno (CAR) and α-Humuleno (HUM) are the primary constituents of the copaiba oleoresin species. These natural products are primarily used by the Amazonian population and marketed as phytotherapies and cosmetics. The aim of this study was to develop and validate a method that simultaneously assays the isomers present in copaiba oleoresins by high performance liquid chromatography using the Box-Behnken design. After preliminary studies, the reverse phase chromatographic system was selected using a cyano column and a mobile phase consisting of acetonitrile and phosphate buffer. The Box-Behnken design was applied at three levels and with four independent variables: flow rate (X 1), gradient slope time (X 2), proportion of organic compounds at the end of the gradient (X 3) and at the beginning of the gradient (X 4). Also, the responses of the dependent variables: CAR retention time (Y 1) and the resolution between the CAR and HUM peaks (Y 2) was assessed. The mathematical model obtained from the regression results was satisfactory (R 2 >0.98, n =27) and showed a quadratic relationship where the effects of interactions between the variables, was observed by response surface graphs. The simultaneous optimization method was used to establish the best compromise of the resolution between the CAR and HUM isomers while adjusting the retention time of CAR. This method was successfully optimized by BBD obtaining chromatographic peaks with good symmetry, resolution and separation efficiency. The validation of the developed method confirmed its specificity, precision, accuracy and linearity in the range of 5.0–11.0 and 0.4–1.0μg/mL for CAR and HUM, respectively, and is considered suitable for routine applications which assure quality control.
Liquid chromatography–mass spectrometric determination of rufinamide in low volume plasma samples
18 October 2013,
10:35:40
Publication date: 1 December
2013
Source:Journal of Chromatography B, Volume 940
Author(s): Zsolt Gáll , Szende Vancea , Maria T. Dogaru , Tibor Szilágyi
Quantification of rufinamide in plasma was achieved using a selective and sensitive liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) method. The chromatographic separation was achieved on a reversed phase column (Zorbax SB-C18 100mm×3mm, 3.5μm) under isocratic conditions. The mobile phase consisted of a mixture of water containing 0.1% formic acid and methanol (50:50, v/v). The mass spectrometric detection of the analyte was in multiple reaction monitoring mode (MRM) using an electrospray positive ionization (ESI positive). The monitored ions were 127 m/z derived from 239 m/z rufinamide and 108 m/z derived from 251 m/z the internal standard (lacosamide). Protein precipitation with methanol was applied for sample preparation using only 50μl aliquots. The concentration range was 40–2000ng/ml for rufinamide in plasma. The limit of detection was 1.25ng/ml and the lower limit of quantification was established at 5ng/ml rufinamide concentration. Selectivity and matrix effect was verified using individual human, rat and rabbit plasma samples. Short-term, post-preparative and freeze–thaw stability was also investigated. The proposed method provides accuracy, precision and high-throughput (short runtime 4.5min) for quantitative determination of rufinamide in plasma. This is the first reported liquid chromatography–tandem mass spectrometric (LC–MS/MS) method for analysis of rufinamide from low volume plasma samples. The LC–MS/MS method was validated according to the current official guidelines and can be applied to accurately measure rufinamide level of large number of plasma samples from clinical studies or therapeutic drug monitoring.
Source:Journal of Chromatography B, Volume 940
Author(s): Zsolt Gáll , Szende Vancea , Maria T. Dogaru , Tibor Szilágyi
Quantification of rufinamide in plasma was achieved using a selective and sensitive liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) method. The chromatographic separation was achieved on a reversed phase column (Zorbax SB-C18 100mm×3mm, 3.5μm) under isocratic conditions. The mobile phase consisted of a mixture of water containing 0.1% formic acid and methanol (50:50, v/v). The mass spectrometric detection of the analyte was in multiple reaction monitoring mode (MRM) using an electrospray positive ionization (ESI positive). The monitored ions were 127 m/z derived from 239 m/z rufinamide and 108 m/z derived from 251 m/z the internal standard (lacosamide). Protein precipitation with methanol was applied for sample preparation using only 50μl aliquots. The concentration range was 40–2000ng/ml for rufinamide in plasma. The limit of detection was 1.25ng/ml and the lower limit of quantification was established at 5ng/ml rufinamide concentration. Selectivity and matrix effect was verified using individual human, rat and rabbit plasma samples. Short-term, post-preparative and freeze–thaw stability was also investigated. The proposed method provides accuracy, precision and high-throughput (short runtime 4.5min) for quantitative determination of rufinamide in plasma. This is the first reported liquid chromatography–tandem mass spectrometric (LC–MS/MS) method for analysis of rufinamide from low volume plasma samples. The LC–MS/MS method was validated according to the current official guidelines and can be applied to accurately measure rufinamide level of large number of plasma samples from clinical studies or therapeutic drug monitoring.
Stereoselective analysis of nebivolol isomers in human plasma by high-performance liquid chromatography–tandem mass spectrometry: Application in pharmacokinetics
18 October 2013,
10:35:40
Publication date: 1 December
2013
Source:Journal of Chromatography B, Volume 940
Author(s): Daniel Valente Neves , Carolina Pinto Vieira , Eduardo Barbosa Coelho , Maria Paula Marques , Vera Lucia Lanchote
Nebivolol is available for clinical use as a racemic mixture. Isomer d-nebivolol (SRRR) is a β1 adrenergic receptor blocker and its antipode, l-nebivolol (RSSS) is responsible for endothelium-dependent NO liberation. This report describes the development and validation of a method of analysis of nebivolol isomers in human plasma by high-performance liquid chromatography–tandem mass spectrometry (LC–MS/MS). Nebivolol isomers were extracted from 2mL aliquots of plasma spiked with tramadol as internal standard, alkalinized and added of sodium chloride and diisopropyl ether:dichloromethane (70:30, v/v). Nebivolol isomers were resolved on a Chirobiotic® V column using methanol:acetic acid:diethylamine (100:0.15:0.05, v/v/v) as mobile phase. Protonated ion and respective ion product were monitored in transitions 406>151 for nebivolol and 264>58 for internal standard tramadol. There was no racemization of nebivolol isomers during the procedures of sample preparation and chromatographic analysis and matrix effect was absent. Analysis of nebivolol isomers showed linearity for plasma concentrations of 25–2500pg/mL of each isomer. The quantification limit was 25pg of each isomer/mL of plasma. Variation coefficients and inaccuracy calculated in precision and accuracy determinations were lower than 15%. Nebivolol was stable in human plasma after three successive cycles of freezing and thawing, during 4h at room temperature and after processing during 12h in the auto sampler at 5°C showing deviation values lower than 15%. The method was applied in a study of the kinetic disposition of nebivolol in plasma samples collected until 48h after administration of an oral single dose of 10mg of racemic nebivolol hydrochloride to a patient with systemic arterial hypertension. The clinical study demonstrated that the nebivolol pharmacokinetics is stereoselective. Isomer l-nebivolol showed higher AUC0–∞ (9.4ng/h/mL vs. 4.7ng/h/mL) and smaller apparent clearance (Cl/f) (531.8L/h vs. 1304.4L/h) when compared to antipode d-nebivolol.
Source:Journal of Chromatography B, Volume 940
Author(s): Daniel Valente Neves , Carolina Pinto Vieira , Eduardo Barbosa Coelho , Maria Paula Marques , Vera Lucia Lanchote
Nebivolol is available for clinical use as a racemic mixture. Isomer d-nebivolol (SRRR) is a β1 adrenergic receptor blocker and its antipode, l-nebivolol (RSSS) is responsible for endothelium-dependent NO liberation. This report describes the development and validation of a method of analysis of nebivolol isomers in human plasma by high-performance liquid chromatography–tandem mass spectrometry (LC–MS/MS). Nebivolol isomers were extracted from 2mL aliquots of plasma spiked with tramadol as internal standard, alkalinized and added of sodium chloride and diisopropyl ether:dichloromethane (70:30, v/v). Nebivolol isomers were resolved on a Chirobiotic® V column using methanol:acetic acid:diethylamine (100:0.15:0.05, v/v/v) as mobile phase. Protonated ion and respective ion product were monitored in transitions 406>151 for nebivolol and 264>58 for internal standard tramadol. There was no racemization of nebivolol isomers during the procedures of sample preparation and chromatographic analysis and matrix effect was absent. Analysis of nebivolol isomers showed linearity for plasma concentrations of 25–2500pg/mL of each isomer. The quantification limit was 25pg of each isomer/mL of plasma. Variation coefficients and inaccuracy calculated in precision and accuracy determinations were lower than 15%. Nebivolol was stable in human plasma after three successive cycles of freezing and thawing, during 4h at room temperature and after processing during 12h in the auto sampler at 5°C showing deviation values lower than 15%. The method was applied in a study of the kinetic disposition of nebivolol in plasma samples collected until 48h after administration of an oral single dose of 10mg of racemic nebivolol hydrochloride to a patient with systemic arterial hypertension. The clinical study demonstrated that the nebivolol pharmacokinetics is stereoselective. Isomer l-nebivolol showed higher AUC0–∞ (9.4ng/h/mL vs. 4.7ng/h/mL) and smaller apparent clearance (Cl/f) (531.8L/h vs. 1304.4L/h) when compared to antipode d-nebivolol.
MCM-41 solid phase membrane tip extraction combined with liquid chromatography for the determination of non-steroidal anti-inflammatory drugs in human urine
18 October 2013,
10:35:40
Publication date: 1 December
2013
Source:Journal of Chromatography B, Volume 940
Author(s): Sazlinda Kamaruzaman , Mohd Marsin Sanagi , Salasiah Endud , Wan Aini Wan Ibrahim , Noorfatimah Yahaya
Mesoporous silica material, MCM-41, was utilized for the first time as an adsorbent in solid phase membrane tip extraction (SPMTE) of non-steroidal anti-inflammatory drugs (NSAIDs) in urine prior to high performance liquid chromatography-ultraviolet (HPLC-UV) analysis. The prepared MCM-41 material was enclosed in a polypropylene membrane tip and used as an adsorbent in SPMTE. Four NSAIDs namely ketoprofen, diclofenac, mefenamic acid and naproxen were selected as model analytes. Several important parameters, such as conditioning solvent, sample pH, salting-out effect, sample volume, extraction time, desorption solvent and desorption time were optimized. Under the optimum extraction conditions, the MCM-41-SPMTE method showed good linearity in the range of 0.01–10μg/mL with excellent correlation coefficients (r =0.9977–0.9995), acceptable RSDs (0.4–9.4%, n =3), good limits of detection (5.7–10.6μg/L) and relative recoveries (81.4–108.1%). The developed method showed a good tolerance to biological sample matrices.
Source:Journal of Chromatography B, Volume 940
Author(s): Sazlinda Kamaruzaman , Mohd Marsin Sanagi , Salasiah Endud , Wan Aini Wan Ibrahim , Noorfatimah Yahaya
Mesoporous silica material, MCM-41, was utilized for the first time as an adsorbent in solid phase membrane tip extraction (SPMTE) of non-steroidal anti-inflammatory drugs (NSAIDs) in urine prior to high performance liquid chromatography-ultraviolet (HPLC-UV) analysis. The prepared MCM-41 material was enclosed in a polypropylene membrane tip and used as an adsorbent in SPMTE. Four NSAIDs namely ketoprofen, diclofenac, mefenamic acid and naproxen were selected as model analytes. Several important parameters, such as conditioning solvent, sample pH, salting-out effect, sample volume, extraction time, desorption solvent and desorption time were optimized. Under the optimum extraction conditions, the MCM-41-SPMTE method showed good linearity in the range of 0.01–10μg/mL with excellent correlation coefficients (r =0.9977–0.9995), acceptable RSDs (0.4–9.4%, n =3), good limits of detection (5.7–10.6μg/L) and relative recoveries (81.4–108.1%). The developed method showed a good tolerance to biological sample matrices.
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