A high-sensitivity LC-MS/MS method for the determination of 4-methyl-piperazine-1-carbodithioc acid 3-cyano-3, 3-diphenylpropyl ester hydrochloride in rat plasma and its application to a pharmacokinetics study

4‐Methyl‐piperazine‐1‐carbodithioc acid 3‐cyano‐3, 3‐diphenylpropyl ester hydrochloride (TM208), a newly synthesized anticancer compound, was quantified using liquid chromatography–tandem mass spectrometry (LC‐MS/MS) for the first time. A simple, rapid and sensitive assay method using propranolol as internal standard (IS) after one‐step precipitation with acetonitrile was developed and validated to determine TM208 in rat plasma. Separation was achieved on a reverse‐phase C₁₈ column with a mobile phase composed of methanol–water (pH4.0) containing 5 m m ammonium acetate in gradient elution mode. A triple quadrupole tandem mass spectrometer with electrospray ionization source was used as detector and operated by multiple reaction monitoring in the positive ion mode. Calibration curves were linear (r > 0.99) between 0.2 and 500 ng/mL. The quantitative limit was 0.2 ng/mL; reliable precision and accuracy were validated by relative standard deviation values in the range 3.44–13.15% and relative error values between ?0.58 and ?9.78%. The method was successfully applied to preclinical pharmacokinetic studies of TM208. Copyright © 2011 John Wiley & Sons, Ltd.     

Quantification of an antitumor agent (copen) in rat plasma by liquid chromatography–electrospray ionization tandem mass spectrometry and its application in a preclinical pharmacokinetic study

Copen is a derivative obtained from the structural modification of osthole, which inhibits tumoral proliferation in many tumor cell lines. A rapid and sensitive liquid chromatography–tandem mass spectrometry (LC‐MS/MS) method was established for the quantification of copen in rat plasma. After a simple sample preparation procedure by one‐step protein precipitation with methanol, copen and bicalutamide (internal standard, IS) were chromatographed on a Zorbax SB‐C₁₈ (4.6×100 mm, 1.8 µm) column with a mobile phase consisting of methanol–5 mm ammonium formate water with 0.1% formic acid (80:20, v/v). MS detection was performed on a triple quadrupole tandem mass spectrometer in the multiple reaction monitoring mode with a positive eletrospray ionization source. The assay was validated in the concentration range of 51.58–20630 ng/mL, with a limit of quantitation (LOQ) of 51.58 ng/mL. The intra‐ and inter‐day precisions (relative standard deviation) were ≤3.21 and ≤11.3%, respectively, with accuracy (%) in the range of 94.66–102.1%. The method was fully validated in a study of the pharmacokinetics of copen (25 mg/kg) after intragastric administration in rats. Copyright © 2014 John Wiley & Sons, Ltd.     

Quantitative determination of meloxicam in dog plasma by high performance liquid chromatography–tandem mass spectrometry and its application in a pharmacokinetic study

A rapid, selective and sensitive high‐performance liquid chromatography–tandem mass spectrometry (HPLC‐MS/MS) method was developed to determine meloxicam in beagle dog plasma. Sample pretreatment involved a one‐step protein precipitation with methanol of 0.1 mL plasma. Analysis was performed on a Venusil ASB‐C₁₈ column with mobile phase consisting of methanol–water (containing 0.1% formic acid) (75:25, v/v). The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring mode via electrospray ionization source. Each plasma sample was chromatographed within 4.1 min. The linear calibration curves for meloxicam was obtained in the concentration range of 10.3–4.12 × 10³ ng/mL (r ≥ 0.99). The intra‐ and inter‐day precisions (relative standard deviation) were ≤ 15%, and accuracy (relative error) was within ±7.3%. The method herein described was fully validated and successfully applied to the pharmacokinetic study of meloxicam tablets in beagle dog.     

Quantitation of unbound sunitinib and its metabolite N-desethyl sunitinib (SU12662) in human plasma by equilibrium dialysis and liquid chromatography-tandem mass spectrometry: application to a pharmacokinetic study

A rapid, selective, and sensitive liquid chromatography–tandem mass spectrometry method was developed and validated for the simultaneous determination of unbound sunitinib and its active metabolite N‐desethyl sunitinib in plasma. Plasma and post‐dialysis buffer samples were extracted using a liquid–liquid extraction procedure with acetonitrile–n‐butylchloride (1:4, v/v). Chromatographic separation was achieved on a Waters X‐Terra® MS RP₁₈ column with a mobile phase consisting of acetonitrile and water (60:40, v/v) containing formic acid (0.1%, v/v) using an isocratic run, at a flow‐rate of 0.2 mL/min. Analytes were detected by electrospray tandem mass spectrometry in the selective reaction monitoring mode. Linear calibration curves were generated over the ranges 0.1–100 and 0.02–5 ng/mL for sunitinib and 0.2–200 and 0.04–10 ng/mL for N‐desethyl sunitinib in plasma and in phosphate‐buffered solution, respectively. The values for both within‐day and between‐day precision and accuracy were well within the generally accepted criteria for analytical methods. The analytical range was sufficient to determine the unbound and total concentrations of both analytes. The method was applied for measurement unbound concentrations in addition to total concentrations of sunitinib and its metabolite in plasma of a cancer patient receiving 50 mg daily dose. Copyright © 2012 John Wiley & Sons, Ltd.     

Determination of aripiprazole in rat plasma and brain using ultra-performance liquid chromatography/electrospray ionization tandem mass spectrometry

Aripiprazole is an important antipsychotic drug. A simple, sensitive and rapid ultra‐performance liquid chromatography/electrospray ionization tandem mass spectrometry (UPLC‐ESI‐MS/MS) method was developed and validated for the simultaneous quantification of this compound in rat plasma and brain homogenate. The analyte was extracted from rat plasma and brain homogenate using a weak cation exchange mixed‐mode resin‐based solid phase extraction. The compound was separated on an Agilent Eclipse Plus C₁₈ (2.1 × 50 mm, 1.8 µm) column using a mobile phase of (A) 0.1% formic acid aqueous and (B) acetonitrile with gradient elution. The analyte was detected in positive ion mode using multiple reaction monitoring. The method was validated and the specificity, linearity, limit of quantitation (LOQ), precision, accuracy, recoveries and stability were determined. The LOQ was 0.5 ng/mL for aripiprazole in plasma and 1.5 ng/g in brain tissue. The MS response was linear over the concentration range 0.5–100 ng/mL for aripiprazole in plasma and 1.5–300 ng/g in brain tissue. The precision and accuracy for intra‐day and inter‐day were better than 14%. The relative and absolute recoveries were above 72% and the matrix effects were low. This validated method was successfully used to quantify the rat plasma and brain tissue concentrations of the analyte following chronic treatment with aripiprazole. Copyright © 2012 John Wiley & Sons, Ltd.     

An LC‐MS/MS method for determination of calceorioside B with cardiomyocyte protective activity in rat plasma and application to a pharmacokinetic study

A simple, sensitive and rapid liquid chromatography–tandem mass spectrometry (LC‐MS/MS) method was developed and validated for the determination of calceorioside B (CLB) in rat plasma. Detection was performed on a Thermo Scientific Hypersil Gold chromatography column using isocratic elution with a mobile phase of methanol–5 m m ammonium acetate–formic acid (70:30:0.1, v/v/v). Mass spectrometry was performed in selection reaction monitoring mode using a positive electrospray ionization interface. Good linearity was found for CLB in plasma in the linear range of 1.00–500 ng/mL (r > 0.9960). The validated method was successfully applied to the pharmacokinetic study of CLB in rats. Copyright © 2015 John Wiley & Sons, Ltd.     

Quantitative determination of rupestonic acid in rat plasma by high‐performance liquid chromatography–tandem mass spectrometry and its application in a pharmacokinetic study

A sensitive and specific high‐performance liquid chromatography–electrospray ionization–tandem mass spectrometry (HPLC‐ESI‐MS/MS) method was developed and validated for determination of rupestonic acid in rat plasma. Protein precipitation method was used to extract rupestonic acid and the internal standard (IS) warfarin sodium from rats plasma. The chromatographic separation was performed on an Agela Venusil XBP Phenyl column with an isocratic mobile phase consisting of methanol–0.1% formic acid in water (40:60, v/v), pumped at 0.4 mL/min. Rupestonic acid and the internal standard (IS) warfarin sodium were detected at m/z 247.2 → 203.1 and 307.1 → 161.3 in positive ion and multiple reaction monitoring mode respectively. The standard curves were linear over the concentration range of 2.5–5000 ng/mL (r² > 0.99). The within‐day and between‐day precision values for rupestonic acid at four concentrations were 4.7–5.7 and 4.4–8.7%, respectively. The method described herein was fully validated and successfully applied to the pharmacokinetic study after an intravenous administration of rupestonic acid in rats. Copyright © 2012 John Wiley & Sons, Ltd.     

Quantification and pharmacokinetic study of entrectinib in rat plasma using ultra‐performance liquid chromatography tandem mass spectrometry

To characterize the preclinical plasma pharmacokinetics of entrectinib, a reproducible and precise assay is necessary. In this study, we developed and validated a simple ultra‐performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) method for the measurement of entrectinib using carbamazepine as the internal standard in rat plasma. Sample preparation was a simple protein precipitation with acetonitrile, then entrectinib was eluted on an Acquity UPLC BEH C₁₈ column (2.1 × 50 mm, 1.7 μm) using a gradient elution with a mobile phase composed of acetonitrile (A) and 0.1% formic acid in water (B). Detection was achieved using multiple‐reaction monitoring in positive ion electrospray ionization mode. The method showed good linearity over the concentration range of 1–250 ng/mL (r² > 0.9951). The intra‐ and inter‐day precision was determined with the values of 6.3–12.9 and 2.6–6.9%, respectively, and accuracy values of 0.5–11.6%. Matrix effect, extraction recovery, and stability data all met the acceptance criteria of US Food and Drug Administration guidelines for bioanalytical method validation. The method was successfully applied to a pharmacokinetic study. In this study, we developed the complete validated method for the quantification of entrectinib in rat plasma.     

Simultaneous quantification of olanzapine and its metabolite N‐desmethylolanzapine in human plasma by liquid chromatography tandem mass spectrometry for therapeutic drug monitoring

A simple, sensitive, and selective liquid chromatography tandem mass spectrometry (LC‐MS/MS) method was developed and validated for the simultaneous quantification of olanzapine (OLZ) and its metabolite N‐desmethylolanzapine (DMO) in human plasma for therapeutic drug monitoring. Sample preparation was performed by one‐step protein precipitation with methanol. The analytes were chromatographed on a reversed‐phase YMC‐ODS‐AQ C₁₈ Column (2.0 × 100 mm,3 µm) by a gradient program at a flow rate of 0.30 mL/min. Quantification was performed on a triple quadrupole tandem mass spectrometer via electrospray ionization in positive ion mode. The method was validated for selectivity, linearity, accuracy, precision, matrix effect, recovery and stability. The calibration curve was linear over the concentration range 0.2–120 ng/mL for OLZ and 0.5–50 ng/mL for DMO. Intra‐ and interday precisions for OLZ and DMO were <11.29%, and the accuracy ranged from 95.23 to 113.16%. The developed method was subsequently applied to therapeutic drug monitoring for psychiatric patients receiving therapy of OLZ tablets. The method seems to be suitable for therapeutic drug monitoring of patients undergoing therapy with OLZ and might contribute to prediction of the risk of adverse reactions. Copyright © 2014 John Wiley & Sons, Ltd.     

LC-MS/MS determination and pharmacokinetic study of albiflorin and paeoniflorin in rat plasma after oral administration of Radix Paeoniae Alba extract and Tang-Min-Ling-Wan

A rapid, sensitive and selective liquid chromatography/tandem mass spectrometry method (LC‐MS/MS) was developed and validated for simultaneous determination of albiflorin and paeoniflorin in rat plasma using geniposide as an internal standard. Plasma samples were extracted by solid‐phase extraction. Chromatographic separation was carried out on a Zorbax SB‐C₁₈ analytical column (150 × 2.1 mm × 5 µm) with 0.1% formic acid–acetonitrile (70:30, v/v) as the mobile phase. Detection was performed by multiple reaction monitoring mode using electrospray ionization in the positive ion mode. The total run time was 3.0 min between injections. The calibration curves were linear over a range of 1–1000 ng/mL for albiflorin and 2–2000 ng/mL for paeoniflorin. The overall precision and accuracy for all concentrations of quality controls and standards were better than 15%. Mean recovery was determined to be 87.7% for albiflorin and 88.8% for paeoniflorin. The validated method was successfully applied to the pharmacokinetic study of albiflorin and paeoniflorin in rat plasma after oral administration of Radix Paeoniae Alba extract and Tang‐Min‐Ling‐Wan. The pharmacokinetic parameters showed that albiflorin and paeoniflorin from Tang‐Min‐Ling‐Wan were absorbed more rapidly with higher concentrations in plasma than that from Radix Paeoniae Alba extract. The results provided a meaningful basis for evaluating the clinical applications of traditional Chinese medicine. Copyright © 2010 John Wiley & Sons, Ltd.     

A simple,rapid and reliable liquid chromatography–mass spectrometry method for determination of methotrexate in human plasma and its application to therapeutic drug monitoring

A simple, rapid and reliable liquid chromatography–electrospray ionization tandem mass spectrometry method was established and validated for the determination of methotrexate in human plasma. After a straightforward protein precipitation by acetonitrile–water (70:30, v/v), methotrexate (MTX) and p‐aminoacetophenone (used as internal standard, IS) were separated on a Column C₁₈ column (50 × 2.1 mm, 3 µm; Column Technology, Fremont, CA, USA) using a gradient elution with mobile phase of acetonitrile and 0.03% acetic acid aqueous solution at a flow rate of 0.5 mL/min. The total chromatographic runtime was 5 min for each injection. Quantification detection was performed in a triple‐quadruple tandem mass spectrometer under positive mode monitoring the following mass transitions: m/z 455.3 → 308.3 for MTX and m/z 136.1 → 94.4 for IS. The calibration curve was linear over the range of 0.05–25.0 µmol/L with a lower limit of quantification of 0.05 µmol/L. The intra‐ and interday precisions were <5.2%, the accuracy varied from ?4.1 to 4.5%. The recovery was >94%. The LC‐MS/MS method showed an excellent agreement with the existing HPLC‐UV method using Passing–Bablok regression and Bland–Altman difference plot analysis. The validated LC‐MS/MS can be successfully applied to the routine therapeutic drug monitoring of MTX in clinical laboratories. Copyright © 2015 John Wiley & Sons, Ltd.     

Study the pharmacokinetics of AV-45 in rat plasma and metabolism in liver microsomes by ultra-performance liquid chromatography with mass spectrometry

An ultra‐performance liquid chromatography–tandem mass spectrometric (UPLC‐MS/MS) method was developed and validated to determine AV‐45 in rat plasma. After the addition of the internal standard benzophenone, plasma samples were pretreated by protein precipitation. Chromatographic separation was achieved on an Acquity UPLC BEH C₁₈ column (50 × 2.1 mm, 1.7 µm) by gradient elution at a flow rate of 0.4 mL/min. Detection of analytes and internal standard (IS) was done by tandem mass spectrometry, operating in positive‐ion and multiple reaction monitoring mode. The method was fully validated for its sensitivity, selectivity, accuracy and precision, matrix effect and stability study. The calibration curve showed good linearity over the concentration range 2.00–1000 ng/mL for AV‐45. Intra‐ and inter‐day precisions were less than 7.6%, and accuracy ranged from 100.6 to 107.8%. There was no matrix effect. The validated method was successfully applied to a pharmacokinetic study of AV‐45 in rats. Additionally, the metabolism of AV‐45 in rat liver microsomes was also studied by ultra‐performance liquid chromatography combined with time‐of‐flight mass spectrometry (UPLC/TOF‐MS). With the help of chromatographic behavior and accurate mass measurements, the metabolites were characterized. Copyright © 2011 John Wiley & Sons, Ltd.     

A liquid chromatography-tandem mass spectrometry assay for the determination of nemonoxacin (TG-873870), a novel nonfluorinated quinolone, in human plasma and urine and its application to a single-dose pharmacokinetic study in healthy Chinese volunteers

Nemonoxacin (TG‐873870) is a novel C‐8‐methoxy nonfluorinated quinolone with higher activity than ciprofloxacin, levofloxacin and moxifloxacin against Gram‐positive pathogens including methicillin‐susceptible or methicillin‐resistant Staphylococcus aureus and Streptococcus pneumoniae with various resistant phenotypes. A rapid, sensitive and selective liquid chromatography–tandem mass spectrometric (LC‐MS/MS) method was developed and validated to determine the concentration of nemonoxacin in human plasma and urine. Protein precipitation and liquid–liquid extraction were employed for plasma and urine sample preparations, respectively, and extract was then injected into the system. Separation was performed on a C₁₈ reversed‐phase column using acetonitrile–0.1% formic acid as a mobile phase. Both analyte and internal standard (gatifloxacin) were determined using electrospray ionization and the MS data acquisition via the selected reaction monitoring in positive‐ion mode. The lower limit of quantification was 5 ng/mL and the calibration curves were linear in the concentration range of 5–1000 ng/mL. The accuracy, precision, selectivity, linearity, recovery, matrix effect and stability were validated for TG‐873870 in human plasma and urine. The method was successfully applied to a pharmacokinetic study enrolling 12 healthy Chinese volunteers administered nemonoxacin malate capsules. Copyright © 2012 John Wiley & Sons, Ltd.     

An improved LC‐MS/MS method for simultaneous determination of 1,5‐dicaffeoylquinic acid and its active metabolites in human plasma and its application to a pharmacokinetic study in patients

In this study, a sensitive, selective and reproducible liquid chromatography–tandem mass spectrometry method for the simultaneous determination of 1,5‐dicaffeoylquinic acid (1,5‐DCQA) and its active metabolites, 1‐caffeoyl‐5‐feruoylquinic acid and 1,5‐O‐diferuoylquinic acid, in human plasma, using puerarin as internal standard, was developed and validated. Analytes were extracted from plasma samples by liquid–liquid extraction with ethyl acetate, separated on a C₁₈ reversed‐phase column with water containing 5 mM ammonium acetate and acetonitrile as the mobile phase and detected by electrospray ionization mass spectrometry in negative selected reaction monitoring mode. The accuracy and precision of the method were acceptable and linearity was good over the range 1–200 ng/mL for each analyte. In addition, the selectivity, extraction recovery and matrix effect were satisfactory too. The validated LC‐MS/MS method was successfully applied to phase II clinical pharmacokinetic study of 1,5‐DCQA in patients. Copyright © 2010 John Wiley & Sons, Ltd.     

Quantification of polygalasaponin F in rat plasma using liquid chromatography–tandem mass spectrometry and its pharmacokinetics application

A rapid and highly selective liquid chromatography–tandem mass spectrometric (LC‐MS/MS) method for determination of polygalasaponin F (PF) in rat plasma was developed and validated. The chromatographic separation was achieved on a reverse‐phase Zorbax SB‐C₁₈ column (150 × 4.6 mm, 5 µm), using 2 mm ammonium acetate (pH adjusted to 6.0 with acetic acid) and acetonitrile (25:75, v/v) as a mobile phase at 30 °C. MS/MS detection was performed using an electrospray ionization operating in positive ion multiple reaction monitoring mode by monitoring the ion transitions from m/z 1091.5 → 471.2 (PF) and m/z 700.4 → 235.4 (internal standard), respectively. The calibration curve showed a good linearity in the concentration range 0.0544–13.6 µg/mL, with a limit of quantification of 0.0544 µg/mL. The intra‐ and inter‐day precisions were <9.7% in rat plasma. The method was validated as per US Food and Drug Administration guidelines and successfully applied to pharmacokinetic study of PF in rats. Copyright © 2015 John Wiley & Sons, Ltd.     

Simultaneous determination of aurantio‐obtusin,chrysoobtusin, obtusin and 1‐desmethylobtusin in rat plasma by UHPLC‐MS/MS

A sensitive and reliable ultra‐high‐performance liquid chromatography–electrospray ionization–tandem mass spectrometry (UHPLC‐MS/MS) method was developed and validated for the simultaneous determination of four active components of Semen Cassiae extract (aurantio‐obtusin, chrysoobtusin, obtusin and 1‐desmethylobtusin) in rat plasma after oral administration. Chromatographic separation was achieved on an Agilent Poroshell 120 C₁₈ column with gradient elution using a mobile phase that consisted of acetonitrile‐ammonium acetate in water (30 mm ) at a flow rate of 0.4 mL/min. Detection was performed by a triple‐quadrupole tandem mass spectrometer in multiple reaction monitoring mode. The calibration curve was linear over a range of 3.24–1296 ng/mL for aurantio‐obtusin, 0.77–618 ng/mL for chrysoobtusin, 34.55–1818 ng/mL for obtusin and 1.86–1485 ng/mL for 1‐desmethylobtusin. Inter‐ and intra‐day assay variation was <15%. All analytes were shown to be stable during all sample storage and analysis procedures. Copyright © 2013 John Wiley & Sons, Ltd.     

A sensitive and specific liquid chromatography/tandem mass spectrometry method for determination of pinaverium bromide in human plasma: application to a pharmacokinetic study in healthy volunteers

A sensitive and specific method using liquid chromatography–electrospray tandem mass spectrometry (LC‐MS/MS) for the determination of pinaverium bromide in human plasma was developed and validated. Pinaverium bromide and an internal standard (paclitaxel) were isolated from plasma samples by precipitating plasma, and determined by LC‐MS/MS in multiple‐reaction monitoring mode. The main metabolite of pinaverium bromide and endogenous substances in plasma did not show any interference. The calibration curve was linear over the plasma concentration range of 10.0–10000.0 pg/mL with a correlation coefficient of 0.9979. The relative standard derivations intra‐ and inter‐day at 30.0, 300.0 and 8000.0 pg/mL in plasma were less than 15%. The absolute recoveries of pinaverium bromide and the internal standard were 99.7–111.7 and 106.2%, respectively. The lower limit of quantitation was 10 pg/mL. The analytical method was successfully applied to study the pharmacokinetics of pinaverium bromide tablets in healthy Chinese volunteers. Copyright © 2011 John Wiley & Sons, Ltd.     

Bioanalytical method development and validation of novel antithrombotic agent S002-333 by LC-MS/MS and its application to pharmacokinetic studies

A rapid, sensitive and simple liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) method using an electrospray ionization (ECI) source for the quantification of novel anti‐thrombotic agent S002‐333 [2‐(4‐methoxy‐benzenesulfonyl)‐2,3,4,9‐tetrahydro‐1H‐β‐carboxylic acid amide] in rabbit plasma was developed and validated. The extraction from plasma was carried out by simple protein precipitation extraction method. The chromatographic separation was performed on an Ultramex Cyno, (150 × 4.6 mm, 5 µm) with a guard column, using acetonitrile–water (75:25,v/v) with flow rate of 0.6 mL/min as the mobile phase. The tandem mass spectrometer was tuned in the multiple reaction monitoring mode to monitor the m/z transitions 386.4/215.4 for S002‐333 and m/z 393.4/171for the internal standard dexamethasone, using positive ion mode. The MS/MS response was linear over the concentration range from 1.56 to 200 ng/mL, with a lower limit of detection of 0.78 ng/mL. The accuracy and precision of the method were within the acceptable limit of ±20% at the lower limit of quantitation and ±15% at other concentrations and showed no significant matrix effect. The validated method can be used in most or all stages of the screening and optimizing process for future method validation of pharmacokinetic studies Copyright © 2010 John Wiley & Sons, Ltd.     

Development of a fast LC‐MS/MS assay for the determination of deferiprone in human plasma and application to pharmacokinetics

A fast and accurate liquid chromatography/tandem mass spectrometric (LC‐MS/MS) assay was first developed and validated for the determination of deferiprone in human plasma. The analytes were extracted with acetonitrile from only 50 μL aliquots of human plasma to achieve the protein precipitation. After extraction, chromatographic separation of analytes in human plasma was performed using a Synergi Fusion‐RP 80A column at 30 °C. The mobile phase consisted of methanol and 0.2% formic acid containing 0.2 mM EDTA (60:40, v/v). The flow rate of the mobile phase was 0.8 mL/min. The total run time for each sample analysis was 4 min. Detection was performed using electrospray ionization in positive ion multiple reaction monitoring mode by monitoring the precursor‐to‐parent ion transitions m/z 140.1 → 53.1 for deferiprone and m/z 143.1 → 98.1 for internal standard. A linear range was established from 0.1 to 20 µg/mL. The limit of detection was determined as 0.05 µg/mL. The validated method was estimated for linearity, recovery, stability, precision and accuracy. Intraday and interday precisions were 4.3–5.5 and 4.6–7.3%, respectively. The recovery of deferiprone was in the range of 80.1–86.8%. The method was successfully applied to a pharmacokinetic study of deferiprone in six thalassemia patients. Copyright © 2012 John Wiley & Sons, Ltd.     

Determination of pseudo‐ginsenoside GQ in human plasma by high performance liquid chromatography–tandem mass spectrometry

A specific, sensitive and rapid method based on high performance liquid chromatography coupled to tandem mass spectrometry (HPLC‐MS/MS) was developed for the determination of pseudo‐ginsenoside GQ in human plasma. Liquid–liquid extraction was used to isolate the analyte from biological matrix followed by injection of the extracts onto a C₈ column with isocratic elution. Detection was carried out on a triple quadrupole tandem mass spectrometer (API‐4000 system) in multiple reaction monitoring mode using negative electrospray ionization. The mobile phase consisted of methanol–10 mm ammonium acetate (90:10, v/v) and the flow rate was 0.3 mL/min. The method was validated over the concentration range of 5.0–5000.0 ng/mL for plasma. Inter‐ and intra‐day precisions (relative standard deviation) were all within 15% and the accuracy (relative error) was ≤9.4%. The lower limit of quantitation was 5.0 ng/mL. The pseudo‐ginsenoside GQ was stable after 8 h at room temperature, 24 h at autosampler and three freeze–thaw cycles (from ?30 to 25 °C). The method was successfully applied to the pharmacokinetic study of pseudo‐ginsenoside GQ in healthy Chinese volunteers. Copyright © 2013 John Wiley & Sons, Ltd.