A new issue of this journal has just been published. To see abstracts of the papers it contains (with links through to the full papers) click here:
Selected papers from the latest issue:
Development and validation of a rapid and sensitive liquid chromatography-tandem mass spectrometry method for benvitimod quantification in human plasma
10 January 2012, 00:43:45
Publication year: 2012
Source: Journal of Chromatography B, Available online 8 January 2012
Libo Zhao, Baoying Zhu, Xin Chen, Genghui Chen, Haibo Chen, ...
Benvitimod is a newly synthesized non-steroid small molecule being developed as a candidate drug for the treatment of inflammatory skin diseases. Here a rapid, sensitive and specific high performance liquid chromatography-tandem mass spectrometry (LC/ESI/MS/MS) method was developed for the determination of benvitimod in human plasma. The samples were alkalified with disodium tetraborate firstly, and thenextracted by methyl tert-butyl ether. Fluorophenyl-benvitimod was used as internal standard (I.S.). Chromatographic separation was performed on an Ultra C18column (150 mm × 2.1 mm, 5.0 μm). The mixed mobile phase delivered at 300 μl/min was CH3CN/H2O, 76.65:23.35 (v/v), containing 0.2 mmol/L NH4COOH. Detection and quantitation was performed by electrospray ionization (ESI) and multiple reaction monitoring (MRM) in the negative ion mode. The most intense [M-H]MRM transition of benvitimod atm/z253.1→211.0 was used for benvitimod quantitation and the transition atm/z270.9→229.2 was used to monitor I.S. The calibration curve was linear within the concentration range of 0.1–10.0 ng/mL (r > 0.99). The lower limit of quantification (LLOQ) was 0.1 ng/mL. The extraction recovery was above 80%. The accuracy expressed as relative error (RE) was less than 1.03%. The intra- and inter-day precisions were less than 11.81%. The freeze–thaw stability was also investigated and it was found that both benvitimod and the I.S. were quite stable. This method is especially useful for the pharmacokinetic study of benvitimod.
Source: Journal of Chromatography B, Available online 8 January 2012
Libo Zhao, Baoying Zhu, Xin Chen, Genghui Chen, Haibo Chen, ...
Benvitimod is a newly synthesized non-steroid small molecule being developed as a candidate drug for the treatment of inflammatory skin diseases. Here a rapid, sensitive and specific high performance liquid chromatography-tandem mass spectrometry (LC/ESI/MS/MS) method was developed for the determination of benvitimod in human plasma. The samples were alkalified with disodium tetraborate firstly, and thenextracted by methyl tert-butyl ether. Fluorophenyl-benvitimod was used as internal standard (I.S.). Chromatographic separation was performed on an Ultra C18column (150 mm × 2.1 mm, 5.0 μm). The mixed mobile phase delivered at 300 μl/min was CH3CN/H2O, 76.65:23.35 (v/v), containing 0.2 mmol/L NH4COOH. Detection and quantitation was performed by electrospray ionization (ESI) and multiple reaction monitoring (MRM) in the negative ion mode. The most intense [M-H]MRM transition of benvitimod atm/z253.1→211.0 was used for benvitimod quantitation and the transition atm/z270.9→229.2 was used to monitor I.S. The calibration curve was linear within the concentration range of 0.1–10.0 ng/mL (r > 0.99). The lower limit of quantification (LLOQ) was 0.1 ng/mL. The extraction recovery was above 80%. The accuracy expressed as relative error (RE) was less than 1.03%. The intra- and inter-day precisions were less than 11.81%. The freeze–thaw stability was also investigated and it was found that both benvitimod and the I.S. were quite stable. This method is especially useful for the pharmacokinetic study of benvitimod.
Highlights
► Validation of a HPLC–MS/MS method for the determination of benvitimod for the first time ► Highly sensitive, with LLOQ of 0.1 ng/ml using only 0.2 ml of plasma ► Applying to a pharmacokinetics study in patients with mild to moderate psoriasis ► Confirming the low absorption of this drugComparison of extraction procedures for assessment of matrix effect for selective and reliable determination of atazanavir in human plasma by LC-ESI-MS/MS
10 January 2012, 00:43:45
Publication year: 2012
Source: Journal of Chromatography B, Available online 8 January 2012
Manish Yadav, Vikas Trivedi, Vivek Upadhyay, Gaurang Shah, Girin A Baxi, ...
A comparative study with three conventional extraction techniques namely protein precipitation (PP), liquid-liquid extraction (LLE) and solid phase extraction (SPE) has been demonstrated to assess the magnitude of matrix interference by post-column analyte infusion and post extraction analyte spiking for the determination of atazanavir from human plasma. Severe ion suppression observed in PP and to a lesser extent in LLE was circumvented by SPE on LiChrosep Sequence extraction cartridge. Based on these observations a selective, rugged and high throughput SPE-LC-MS/MS method has been developed for reliable determination of atazanavir in human plasma. The chromatographic separation was achieved on a Hypersil Gold C18 (50 mm x 4.6 mm, 5 μm) analytical column using 5 mM ammonium formate in water: methanol (10:90,v/v) as the mobile phase under isocratic conditions. The method was validated over a wide dynamic concentration range of 10-6000 ng/mL. The mean relative recovery and absolute matrix effect across quality controls were 84.9 and 93.2% respectively. The precision value for relative matrix effect between eight different lots of plasma, expressed as %CV of the slopes of the calibration lines was 2.41. The stability of atazanavir under different storage conditions varied from -8.4 to 5.4%. The method was successfully applied to a bioequivalence study of 300 mg atazanavir capsule formulation in 24 healthy Indian males under fasting condition.
Source: Journal of Chromatography B, Available online 8 January 2012
Manish Yadav, Vikas Trivedi, Vivek Upadhyay, Gaurang Shah, Girin A Baxi, ...
A comparative study with three conventional extraction techniques namely protein precipitation (PP), liquid-liquid extraction (LLE) and solid phase extraction (SPE) has been demonstrated to assess the magnitude of matrix interference by post-column analyte infusion and post extraction analyte spiking for the determination of atazanavir from human plasma. Severe ion suppression observed in PP and to a lesser extent in LLE was circumvented by SPE on LiChrosep Sequence extraction cartridge. Based on these observations a selective, rugged and high throughput SPE-LC-MS/MS method has been developed for reliable determination of atazanavir in human plasma. The chromatographic separation was achieved on a Hypersil Gold C18 (50 mm x 4.6 mm, 5 μm) analytical column using 5 mM ammonium formate in water: methanol (10:90,v/v) as the mobile phase under isocratic conditions. The method was validated over a wide dynamic concentration range of 10-6000 ng/mL. The mean relative recovery and absolute matrix effect across quality controls were 84.9 and 93.2% respectively. The precision value for relative matrix effect between eight different lots of plasma, expressed as %CV of the slopes of the calibration lines was 2.41. The stability of atazanavir under different storage conditions varied from -8.4 to 5.4%. The method was successfully applied to a bioequivalence study of 300 mg atazanavir capsule formulation in 24 healthy Indian males under fasting condition.
Highlights
► A reliable SPE-LC-ESI-MS/MS is proposed for determination of atazanavir in human plasma. ► A comparative study with PP, LLE and SPE is demonstrated to show the magnitude of ion suppression. ► Matrix effect assessment is done by post-column analyte infusion and post extraction spiking methods. ► The method is practically free from matrix interference based on relative matrix effect in different lots of plasma. ► The application is demonstrated by a bioequivalence study in healthy volunteers and incurred sample reanalysis.A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for monitoring drug exposure in hematopoietic stem cell transplant recipients
10 January 2012, 00:43:45
Publication year: 2012
Source: Journal of Chromatography B, Available online 8 January 2012
Isabelle Laverdière, Patrick Caron, Félix Couture, Éric Lévesque, Chantal Guillemette
A liquid chromatography–tandem mass spectrometry method was developed for the quantification of circulating levels of multiple immunosuppressant drugs including cyclosporine (CsA), tacrolimus, methotrexate (Mtx), prednisone, prednisolone, methylprednisone, total and free mycophenolic acid (MPA), as well as MPA phenolic (MPAG) and acyl (AcMPAG) glucuronide metabolites. Linearity, precision and accuracy were validated within the typical therapeutic range of concentrations for each compound. The assay was linear over 0.125-25 ng/mL for tacrolimus, 1-500 ng/mL for prednisone/methylprednisone, 2 − 400 ng/mL for Mtx, 2 − 1000 ng/mL for prednisolone and from 7.5 to 1500 ng/mL for CsA with the lowest limit of quantification (LLOQ) being 0.125, 1.00, 2.00, 2.00 and 7.5 ng/mL, respectively. The calibration curve concentrations for MPA and MPAG ranged from 50 to 50000 ng/mL (LLOQ: 50 ng/mL) and 10 to 10000 ng/mL (LLOQ: 10 ng/mL) for AcMPAG. Mean recoveries in blood and plasma were 84% ± 5.7%. The method could measure individual drugs with high sensitivity, accuracy (bias ≤14%), and reproducibility (CV ≤12.8%). Its clinical application was validated by measuring levels of these drugs in samples obtained from hematopoietic stem cell transplant recipients treated with combined immunosuppressive drug therapy. Our results indicate that this approach is suitable for simultaneous determination ofin vivolevels of immunosuppressive drugs commonly used in combined therapies.
Source: Journal of Chromatography B, Available online 8 January 2012
Isabelle Laverdière, Patrick Caron, Félix Couture, Éric Lévesque, Chantal Guillemette
A liquid chromatography–tandem mass spectrometry method was developed for the quantification of circulating levels of multiple immunosuppressant drugs including cyclosporine (CsA), tacrolimus, methotrexate (Mtx), prednisone, prednisolone, methylprednisone, total and free mycophenolic acid (MPA), as well as MPA phenolic (MPAG) and acyl (AcMPAG) glucuronide metabolites. Linearity, precision and accuracy were validated within the typical therapeutic range of concentrations for each compound. The assay was linear over 0.125-25 ng/mL for tacrolimus, 1-500 ng/mL for prednisone/methylprednisone, 2 − 400 ng/mL for Mtx, 2 − 1000 ng/mL for prednisolone and from 7.5 to 1500 ng/mL for CsA with the lowest limit of quantification (LLOQ) being 0.125, 1.00, 2.00, 2.00 and 7.5 ng/mL, respectively. The calibration curve concentrations for MPA and MPAG ranged from 50 to 50000 ng/mL (LLOQ: 50 ng/mL) and 10 to 10000 ng/mL (LLOQ: 10 ng/mL) for AcMPAG. Mean recoveries in blood and plasma were 84% ± 5.7%. The method could measure individual drugs with high sensitivity, accuracy (bias ≤14%), and reproducibility (CV ≤12.8%). Its clinical application was validated by measuring levels of these drugs in samples obtained from hematopoietic stem cell transplant recipients treated with combined immunosuppressive drug therapy. Our results indicate that this approach is suitable for simultaneous determination ofin vivolevels of immunosuppressive drugs commonly used in combined therapies.
Highlights
► We developed a LC-MS/MS method for the simultaneous monitoring of multiple immunosuppressive drugs in blood. ► The validated method demonstrates sensitivity, accuracy and reproducibility. ► Its clinical application has been validated in samples from transplant recipients. ► The method is convenient for therapeutic drug monitoring and large-scale studies.LC-MS/MS in Clinical Chemistry
10 January 2012, 00:43:45
Publication year: 2012
Source: Journal of Chromatography B, Available online 8 January 2012
Michael Vogeser, Christoph Seger
Source: Journal of Chromatography B, Available online 8 January 2012
Michael Vogeser, Christoph Seger
Simultaneous quantification of selective serotonin reuptake inhibitors and metabolites in human plasma by liquid chromatography-electrospray mass spectrometry for therapeutic drug monitoring
10 January 2012, 00:43:45
Publication year: 2012
Source: Journal of Chromatography B, Available online 8 January 2012
Nicolas Ansermot, Marlyse Brawand-Amey, Chin B. Eap
A simple and sensitive liquid chromatography-electrospray ionization mass spectrometry method was developed for the simultaneous quantification in human plasma of all selective serotonin reuptake inhibitors (citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline) and their main active metabolites (desmethyl-citalopram and norfluoxetine). A stable isotope-labeled internal standard was used for each analyte, to compensate for the global method variability, including extraction and ionization variations. After sample (250 μl) pre-treatment with acetonitrile (500 μl) to precipitate proteins, a fast solid-phase extraction procedure was performed using mixed mode Oasis MCX 96-well plate. Chromatographic separation was achieved in less than 9.0 min on a XBridge C18 column (2.1 × 100 mm; 3.5 μm) using a gradient of ammonium acetate (pH 8.1; 50 mM) and acetonitrile as mobile phase at a flow rate of 0.3 ml/min. The method was fully validated according to Société Française des Sciences et Techniques Pharmaceutiques protocols and the latest Food and Drug Administration guidelines. Six point calibration curves were used to cover a large concentration range of 1-500 ng/ml for citalopram, desmethyl-citalopram, paroxetine and sertraline, 1-1000 ng/ml for fluoxetine and fluvoxamine, and 2-1000 ng/ml for norfluoxetine. Good quantitative performances were achieved in terms of trueness (84.2-109.6%), repeatability (0.9-14.6%) and intermediate precision (1.8-18.0%) in the entire assay range including the lower limit of quantification. Internal standard-normalised matrix effects were lower than 13%. The accuracy profiles (total error) were mainly included in the acceptance limits of ±30% for biological samples. The method was successfully applied for routine therapeutic drug monitoring of more than 1600 patient plasma samples over 9 months. Theβ-expectation tolerance intervals determined during the validation phase were coherent with the results of quality control samples analyzed during routine use. This method is therefore precise and suitable both for therapeutic drug monitoring and pharmacokinetic studies in most clinical laboratories.
Source: Journal of Chromatography B, Available online 8 January 2012
Nicolas Ansermot, Marlyse Brawand-Amey, Chin B. Eap
A simple and sensitive liquid chromatography-electrospray ionization mass spectrometry method was developed for the simultaneous quantification in human plasma of all selective serotonin reuptake inhibitors (citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline) and their main active metabolites (desmethyl-citalopram and norfluoxetine). A stable isotope-labeled internal standard was used for each analyte, to compensate for the global method variability, including extraction and ionization variations. After sample (250 μl) pre-treatment with acetonitrile (500 μl) to precipitate proteins, a fast solid-phase extraction procedure was performed using mixed mode Oasis MCX 96-well plate. Chromatographic separation was achieved in less than 9.0 min on a XBridge C18 column (2.1 × 100 mm; 3.5 μm) using a gradient of ammonium acetate (pH 8.1; 50 mM) and acetonitrile as mobile phase at a flow rate of 0.3 ml/min. The method was fully validated according to Société Française des Sciences et Techniques Pharmaceutiques protocols and the latest Food and Drug Administration guidelines. Six point calibration curves were used to cover a large concentration range of 1-500 ng/ml for citalopram, desmethyl-citalopram, paroxetine and sertraline, 1-1000 ng/ml for fluoxetine and fluvoxamine, and 2-1000 ng/ml for norfluoxetine. Good quantitative performances were achieved in terms of trueness (84.2-109.6%), repeatability (0.9-14.6%) and intermediate precision (1.8-18.0%) in the entire assay range including the lower limit of quantification. Internal standard-normalised matrix effects were lower than 13%. The accuracy profiles (total error) were mainly included in the acceptance limits of ±30% for biological samples. The method was successfully applied for routine therapeutic drug monitoring of more than 1600 patient plasma samples over 9 months. Theβ-expectation tolerance intervals determined during the validation phase were coherent with the results of quality control samples analyzed during routine use. This method is therefore precise and suitable both for therapeutic drug monitoring and pharmacokinetic studies in most clinical laboratories.
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