Determination of toosendanin in rat plasma by ultra‐performance liquid chromatography–electrospray ionization–mass spectrometry and its application in a pharmacokinetic study

Toosendanin (TSN) is a major triterpenoid existing in Melia toosendan, which has been used as a digestive tract parasiticide and insecticide but with serious hepatotoxicity. An ultra‐performance liquid chromatography–electrospray ionization–mass spectrometry method was developed for determination of TSN in rat plasma. Plasma samples were separated on Acquity UPLC^TM BEH C₁₈ column with acetonitrile and water as flow phase by gradient elution and determined by quadrupole mass spectrometer in negative selective ion monitoring mode. Usolic acid was used as internal standard. The calibration curves were linear over 0.02–3.0 µg/mL for TSN with a lower limit of quantification (LLOQ) of 20 ng/mL in rat plasma. The extraction recoveries of TSN were within 74.3–80.7% with an accuracy of 94.5–108.9%. The intra‐ and inter‐day precision values of the assay at three quality control levels were 8.8–13.8% and <13.9% at LLOQ level, respectively. The method was successfully applied to a pharmacokinetic study of TSN in rats after a single intravenous and oral administration of 2 and 60 mg/kg. The shorter T_max, higher V_d and Cl of TSN after oral administration indicated that TSN could be absorbed, distributed and eliminated quickly in rats in vivo. The absolute bioavailability of TSN after oral administration was 9.9%. Copyright © 2012 John Wiley & Sons, Ltd.     

Quantification and pharmacokinetics of crizotinib in rats by liquid chromatography–tandem mass spectrometry

Crizotinib is a small molecule inhibitor of anaplastic lymphoma kinase (ALK) and can be used to treat ALK‐positive nonsmall‐cell lung cancer. A rapid and simple high‐performance liquid chromatography–tandem mass spectrometry (LC‐MS/MS) method was developed and validated for the quantification of crizotinib in rat plasma using a chemical synthetic compound buspirone as the internal standard (IS). The plasma samples were pretreated by a simple protein precipitation with methanol–acetonitrile (1:1, v/v). Chromatographic separation was successfully achieved on an Agilent Zorbax XDB C₁₈ column (2.1 × 50 mm, 3.5 µm). The gradient elution system was composed of 0.1% formic acid aqueous solution and 0.1% formic acid in methanol solution. The flow rate was set at 0.50 mL/min. The multiple reaction monitoring was based on the transitions of m/z = 450.3 → 177.1 for crizotinib and 386.2 → 122.2 for buspirone (IS). The assay was successfully validated to demonstrate the selectivity, matrix effect, linearity, lower limit of quantification, accuracy, precision, recovery and stability according to the international guidelines. The lower limit of quantification was 1.00 ng/mL in 50 μL of rat plasma. This LC‐MS/MS assay was successfully applied to the quantification and pharmacokinetic study of crizotinib in rats after intravenous and oral administration of crizotinib. The oral absolute bioavailability of crizotinib in rats was 68.6 ± 9.63%. Copyright © 2015 John Wiley & Sons, Ltd.     

Development and validation of a liquid chromatography–tandem mass spectrometry method for quantitation of indomethacin in rat plasma and its application to a pharmacokinetic study in rats

A highly sensitive and rapid bioanalytical method has been developed and validated for the estimation of indomethacin in rat plasma with liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the positive‐ion mode. The assay procedure involves a simple liquid–liquid extraction of indomethacin and phenacetin (internal standard, IS) from rat plasma with acetonitrile. Chromatographic separation was achieved with 0.2% formic acid–acetonitrile (25:75, v/v) at a flow rate of 0.60 mL/min on an Atlantis dC₁₈ column with a total run time 3.0 min. The MS/MS ion transitions monitored were 357.7 → 139.1 for indomethacin and 180.20 → 110.10 for IS. Method validation and pharmacokinetic study plasma analysis were performed as per FDA guidelines and the results met the acceptance criteria. The lower limit of quantitation achieved was 0.51 ng/mL and the linearity was observed from 0.51 to 25.5 ng/mL. The intra‐ and inter‐day precisions were in the range of 1.00–10.2 and 5.88–9.80%, respectively. This novel method has been applied to an oral pharmacokinetic study in rats. Copyright © 2012 John Wiley & Sons, Ltd.     

Determination of chikusetsusaponin V and chikusetsusaponin IV in rat plasma by liquid chromatography–mass spectrometry and its application to a preliminary pharmacokinetic study

A sensitive liquid chromatography–electrospray ionization–mass spectrometry method has been developed and validated for determination of two major bioactive saponins in rat plasma after oral administration of saponins extracted from Rhizoma Panacis Japonici, including chikusetsusaponin V and chikusetsusaponin IV for the first time. Akebia saponin D was used as the internal standard (IS). Plasma samples were prepared by protein precipitation with methanol. A Phenomenex C₁₈ column (150 × 4.6 mm, 4 µm) was used as the analytical column with a mobile phase of acetonitrile and 0.05% aqueous formic acid. Mass spectrometric detection was achieved by single quadrupole mass spectrometer equipped with an electrospray ionization interface operating in negative ionization mode. Calibration curves showed good linearity over the concentration range of 5–500 ng/mL for the two analytes in rat plasma. The lower limit of quantification was 5 ng/mL. The intra‐ and inter‐batch precisions were within 10.3% and accuracy ranged from ?3.9 to 5.4%. The method was validated and successfully applied to the preliminary pharmacokinetic study of chikusetsusaponin V and chikusetsusaponin IV in rat plasma after oral administration of saponins extracted from Rhizoma Panacis Japonici. Copyright © 2013 John Wiley & Sons, Ltd.     

Simultaneous determination of propofol and remifentanil in rat plasma by liquid chromatography–tandem mass spectrometry: application to preclinical pharmacokinetic drug–drug interaction analysis

Propofol (Pro) is an ultra‐short‐acting hypnotic agent used for general anesthesia that has no analgesic properties. Remifentanil (Rem) is an ultra‐short‐acting opioid administered concomitantly as an analgesic with Pro. To evaluate the pharmacokinetic interactions between Pro and Rem, we developed and validated a method combining high‐performance liquid chromatography with tandem mass spectrometry for simultaneous determination of Pro and Rem. The proposed method was successfully used to study the pharmacokinetic interactions of Pro and Rem coadministered to rats. Copyright © 2014 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 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 enzalutamide,an anti‐prostate cancer drug,in rat plasma using liquid chromatography–tandem mass spectrometry,and its application to a pharmacokinetic study

This report details a method using liquid chromatography–tandem mass spectrometry (LC‐MS/MS) that allows one to determine the concentration of an atypical anticancer drug, enzalutamide, in rat plasma. Specifically, this method involves the addition of an acetonitrile and bicalutamide (internal standard) solution to plasma samples. Following centrifugation of this mixture, an aliquot of the supernatant was directly injected into the LC‐MS/MS system. Separation was achieved using a column packed with octadecylsilica (5 µm, 2.1 × 50 mm) with 10 mM ammonium acetate in acetonitrile as the mobile phase; detection was accomplished using MS/MS by multiple‐reaction monitoring via an electrospray ionization source. This method demonstrated a linear standard curve (r = 0.997) over a concentration range of 0.001–1 µg/mL, as well as an intra‐ and inter‐assay precision of 2.7 and 5.1%, respectively, and an accuracy range from 100.8 to 105.6%. The lower limit of quantification was 1.0 ng/mL in 50 μL of rat plasma sample. We also demonstrated that this analytical method could be successfully applied to the pharmacokinetic study of enzalutamide in rats. Copyright © 2014 John Wiley & Sons, Ltd.     

Rapid and efficient method for the quantification of lychnopholide in rat plasma by liquid chromatography–tandem mass spectrometry for pharmacokinetic application

Lychnopholide is a sesquiterpene lactone usually obtained from Lychnophora and Eremanthus species and has pharmacological activities that include anti‐inflammatory and anti‐tumor. Lychnopholide isolated from Eremanthus matogrossenssis was analyzed in this study. The aims of this study were to develop and validate an analytical methodology by LC‐MS/MS and to quantify lychnopholide in rat plasma. Chromatographic separation was achieved on a C₁₈ column using isocratic elution with the mobile phase consisting of methanol and water (containing 0.1% formic acid) at a flow rate of 0.4 mL/min. The detection was performed in multiple‐reaction monitoring mode using electrospray ionization in positive mode. The method validation was performed in accordance with regulatory guidelines and the results met the acceptance criteria. The linear range of detection was 10–200 ng/mL (r > 0.9961). The intra‐ and inter‐day assay variability were <6.2 and <11.7%, respectively. The extraction recovery was approximately 63% using liquid–liquid extraction with chloroform. Lychnopholide was detected in plasma up to 60 min after intravenous administration in rats. This rapid and sensitive method for the analysis of the sesquiterpene lactone lychnopholide in rat plasma can be applied to pharmacokinetic studies of this compound. Copyright © 2016 John Wiley & Sons, Ltd.     

Determination of limonin in dog plasma by liquid chromatography–tandem mass spectrometry and its application to a pharmacokinetic study

A highly sensitive liquid chromatography–tandem mass spectrometry method was developed and validated for the determination of limonin in beagle dog plasma using nimodipine as internal standard. The analyte and internal standard (IS) were extracted with ether followed by a rapid isocratic elution with 10 mm ammonium acetate buffer–methanol (26:74, v/v) on a C₁₈ column (150 × 2.1 mm i.d.) and subsequent analysis by mass spectrometry in the multiple reaction monitoring mode. The precursor to product ion transitions of m/z 469.4 → 229.3 and m/z 417.2 → 122.0 were used to measure the analyte and the IS. The assay was linear over the concentration range of 0.625–100 ng/mL for limonin in dog plasma. The lower limit of quantification was 0.312 ng/mL and the extraction recovery was >90.4% for limonin. The inter‐ and intra‐day precision of the method at three concentrations was less than 9.9%. The method was successfully applied to pharmacokinetic study of limonin in dogs. Copyright © 2012 John Wiley & Sons, Ltd.     

Determination of PF‐04620110, a novel inhibitor of diacylglycerol acyltransferase‐1, in rat plasma using liquid chromatography–tandem mass spectrometry and its application in pharmacokinetic studies

In this study, we developed a method for the determination of PF‐04620110 (2‐{(1r,4r)‐4‐[4‐(4‐amino‐5‐oxo‐7,8‐dihydropyrimido[5,4‐f][1,4]oxazepin‐6(5H)‐yl)phenyl]cyclohexyl}acetic acid), a novel diacylglycerol acyltransferase 1 (DGAT‐1) inhibitor, in rat plasma and validated it using liquid chromatography–tandem mass spectrometry (LC‐MS/MS). Rat plasma samples were processed following a protein precipitation method by using acetonitrile and were then injected into an LC‐MS/MS system for quantification. PF‐04620110 and imipramine (internal standard) were separated using a Hypersil Gold C₁₈ column, with a mixture of acetonitrile and 10 mm ammonium formate (90:10, v/v) as the mobile phase. The ion transitions monitored in positive‐ion mode [M + H]⁺ of multiple‐reaction monitoring were m/z 397.0 → 260.2 for PF‐04620110 and m/z 280.8 → 86.0 for imipramine. The detector response was specific and linear for PF‐04620110 at concentrations within the range 0.05–50 µg/mL and the signal‐to‐noise ratios for the samples were ≥10. The intra‐ and inter‐day precision and accuracy of the method matched the acceptance criteria for assay validation. PF‐04620110 was stable under various processing and/or handling conditions. PF‐04620110 concentrations in the rat plasma samples could be measured up to 24 h after intravenous or oral administration of PF‐04620110, suggesting that the assay is useful for pharmacokinetic studies in rats. Copyright © 2013 John Wiley & Sons, Ltd.     

Determination of bakkenolide A in rat plasma using liquid chromatography/tandem mass spectrometry and its application to a pharmacokinetic study

A sensitive rapid analytical method was established and validated to determine the bakkenolide A (BA) in rat plasma. This method was further applied to assess the pharmacokinetics of BA in rats receiving a single dose of BA. Liquid chromatography tandem mass spectrometry in multiple reaction monitoring mode was used in the method, and costundide was used as internal standard. A simple protein precipitation based on methanol was employed. The combination of a simple sample cleanup and short chromatographic running time (2.4 min) increased the throughput of the method substantially. The method was validated over the range of 1–1000 ng/mL with a correlation coefficient > 0.99. The lower limit of quantification was 1 ng/mL for BA in plasma. Intra‐ and inter‐day accuracies for BA were 93–112% and 103–104%, respectively, and the inter‐day precision was less than 15%. After a single oral dose of 20 mg/kg of BA, the mean peak plasma concentration (C_max) of BA was 234.7 ± 161 ng/mL at 0.25 h. The area under the plasma concentration–time curve (AUC_{0–24 h}) was 535.8 ± 223.7 h·ng/mL, and the elimination half‐life (T_1/2) was 5.0 ± 0.36 h. In case of intravenous administration of BA at a dosage of 2 mg/kg, the area under the plasma concentration–time curve (AUC_{0–24 h}) was 342 ± 98 h?ng/mL, and the elimination half‐life (T_1/2) was 5.8 ± 0.7 h. Based on the results, the oral bioavailability of BA in rats at 20 mg/kg is 15.7%. Copyright © 2012 John Wiley & Sons, Ltd.     

Determination of cyclobenzaprine in human plasma by liquid chromatography-electrospray ionization tandem mass spectrometry and its application in a pharmacokinetic study

A sensitive, rapid and simple liquid chromatography–electrospray ionization mass spectrometry (LC‐ESI‐MS/MS) method was developed for the quantitative determination of cyclobenzaprine in human plasma, to study the pharmacokinetic behavior of cyclobenzaprine capsule in healthy Chinese volunteers. With escitalopram as the internal standard (IS), sample pretreatment involved a one‐step liquid–liquid extraction using saturated sodium carbonate solution and hexane–diethyl ether (3:1, v/v). The separation was performed on an Ultimate XB‐CN column (150 × 2.1 mm, 5 µm). Isocratic elution was applied using acetonitrile–water (40:60, v/v) containing 10 m M ammonium acetate and 0.1% formic acid. The detection was carried out on a triple‐quadrupole tandem mass spectrometer in multiple reaction monitoring mode via electrospray ionization. The ion‐pairs including m/z 276.2–216.2 for cyclobenzaprine and m/z 325.2–109.1 for IS were used for monitoring. Linear calibration curves were obtained over the range of 0.049–29.81 ng/mL with the lower limit of quantification at 0.049 ng/mL. The intra‐ and inter‐day precision showed ≤6.5% relative standard deviation. The established method laid the groundwork for follow‐up studies and provided basis for the clinical administration of cyclobenzaprine. Copyright © 2011 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.     

Determination of eurycomanone in rat plasma using hydrophilic interaction liquid chromatography–tandem mass spectrometry for pharmacokinetic study

In this study, a rapid, sensitive, and reliable hydrophilic interaction liquid chromatography–tandem mass spectrometry (HILIC‐MS/MS) method for the determination of eurycomanone in rat plasma was developed and validated. Plasma samples were pretreated with a protein precipitation method and quercitrin was used as an internal standard (IS). A HILIC silica column (2.1 × 100 mm, 3 μm) was used for hydrophilic‐based chromatographic separation, using the mobile phase of 0.1% formic acid with acetonitrile in gradient elution at a flow rate of 0.25 mL/min. Precursor–product ion pairs for multiple‐reaction monitoring were m /z 409.1 → 391.0 for eurycomanone and m /z 449.1 → 303.0 for IS. The linear range was 2–120 ng/mL. The intra‐ and inter‐day accuracies were between 95.5 and 103.4% with a precision of <4.2%. The developed method was successfully applied to the pharmacokinetic analysis of eurycomanone in rat plasma after oral dosing with pure compound and E. longifolia extract. The C _max and AUC_0–t , respectively, were 40.43 ± 16.08 ng/mL and 161.09 ± 37.63 ng h/mL for 10 mg/kg eurycomanone, and 9.90 ± 3.97 ng/mL and 37.15 ± 6.80 ng h/mL for E. longifolia extract (2 mg/kg as eurycomanone). The pharmacokinetic results were comparable with each other, based on the dose as eurycomanone.     

A simple,rapid and sensitive liquid chromatography–tandem mass spectrometry method for the determination of dienogest in human plasma and its pharmacokinetic applications under fasting

A simple, rapid and sensitive analytical method using liquid chromatography coupled to tandem mass spectrometry (LC‐MS/MS) detection with positive ion electrospray ionization was developed for the determination of dienogest in human K₂EDTA plasma using levonorgestrel d₆ as an internal standard (IS). Dienogest and IS were extracted from human plasma using simple liquid–liquid extraction. Chromatographic separation was achieved on a Zorbax XDB‐Phenyl column (4.6 × 75 mm, 3.5 µm) under isocratic conditions using acetonitrile–5 mm ammonium acetate (70:30, v/v) at a flow rate of 0.60 mL/min. The protonated precursor to product ion transitions monitored for dienogest and IS were at m/z 312.30 → 135.30 and 319.00 → 251.30, respectively. The method was validated with a linearity range of 1.003–200.896 ng/mL having a total analysis time for each chromatograph of 3.0 min. The method has shown tremendous reproducibility with intra‐ and inter‐day precision (coefficient of variation) <3.97 and 6.10%, respectively, and accuracy within ±4.0% of nominal values. The validated method was applied to a pharmacokinetic study in human plasma samples generated after administration of a single oral dose of 2.0 mg dienogest tablets to healthy female volunteers and was proved to be highly reliable for the analysis of clinical samples. Copyright © 2014 John Wiley & Sons, Ltd.     

Development of a liquid chromatography–tandem mass spectrometry method for the determination of Grayanotoxins in rat blood and its application to toxicokinetic study

A sensitive and specific high‐performance liquid chromatography–tandem mass spectrometry (LC‐MS/MS) method was developed for the determination of Grayanotoxin I (GTX I) and Grayanotoxin III (GTX III) in rat whole blood. Grayanotoxins (GTXs) and clindamycin as internal standard (IS) were extracted from rat blood via solid‐phase extraction using PEP solid‐phase extraction cartridges. Chromatographic separation of the analytes was achieved on a Kinetex C₁₈ (100 × 2.1 mm, 2.6 µm) reversed‐phase column using a gradient elution with the mobile phase of 1% acetic acid in water and methanol at a flow rate of 0.2 mL/min. Electrospray ionization mass spectrometry was operated in the positive ion mode with multiple reaction monitoring. The calibration curves obtained were linear over the concentration range of 1–100 ng/mL with a lower limit of quantification of 1 ng/mL for GTXs. The relative standard deviation of intra‐day and inter‐day precision was below 6.8% and accuracy ranged from 94.8 to 106.6%. The analytes were stable in the stability studies. The validated method was successfully applied to the quantification and toxicokinetic study of GTXs in rats for the first time after oral administration of 11.52 mg/kg mad honey and 0.35 mg/kg GTX III, respectively. Copyright © 2014 John Wiley & Sons, Ltd.     

Simultaneous determination of four secoiridoid and iridoid glycosides in rat plasma by ultra performance liquid chromatography–tandem mass spectrometry and its application to a comparative pharmacokinetic study

A simple, reliable and rapid ultra‐performance liquid chromatography–tandem mass spectrometry method was developed and validated for the simultaneous quantification of four secoiridoid (gentiopicroside, swertiamarin, sweroside) and iridoid glycosides (loganic acid), the bio‐active ingredients in rat plasma. After liquid–liquid extraction, chromatographic separation was accomplished on a Shim‐pack XR‐ODS column with a mobile phase consisting of methanol and 0.1% formic acid in water. A triple quadrupole tandem mass spectrometry equipped with an electrospray ionization source was used as detector operating both in positive and negative ionization mode and operated by multiple‐reaction monitoring scanning. The lower limits of quantitation were 0.25–30 ng/mL for all the analytes. Both intra‐day and inter‐day precision and accuracy of analytes were well within acceptance criteria (±15%). The mean extraction recoveries of analytes and internal standard (amygdalin) from rat plasma were all >71.4%. The validated method was successfully applied to a comparative pharmacokinetic study of four analytes in rat plasma between normal and arthritic rats after oral administration of Huo Luo Xiao Ling Dan and Gentiana macrophylla extract, respectively. Results showed significant differences in pharmacokinetic properties of the analytes among the different groups. Copyright © 2015 John Wiley & Sons, Ltd.     

Determination of ecliptasaponin A in rat plasma and tissues by liquid chromatography‐tandem mass spectrometry

A sensitive, rapid and specific high‐performance liquid chromatography tandem mass spectrometry method (HPLC‐MS/MS) was developed to determine ecliptasaponin A in rat plasma and tissues after oral administration. Ginsenoside Rg1 was used as the internal standard (IS). The plasma and tissues samples were prepared by liquid‐liquid extraction with ethyl acetate and separated on an Eclipse Plus C₁₈ column (2.1 mm × 150 mm, 5 µm) at a flow rate of 0.4 mL/min using acetonitrile and water (containing 0.05% acetic acid) as the mobile phase. The tandem mass detection was carried out with eletrospray ionization in negative mode. Quantification was performed by using multiple reaction monitoring (MRM), which monitored the fragmentation of m/z 633.4→587.2 for ecliptasaponin A and m/z 859.4→637.4 for the IS. The calibration curves obtained were linear in different matrices, and the lower limit of quantification (LLOQ) achieved was 0.5 ng/mL both for rat plasma and tissues. The intra‐ and inter‐day precisions were below 15%. This method was successfully applied to pharmacokinetic study of ecliptasaponin A in rat plasma and tissues after oral administration. Copyright © 2015 John Wiley & Sons, Ltd.     

Determination of cefdinir levels in rat plasma and urine by high‐performance liquid chromatography–tandem mass spectrometry: application to pharmacokinetics after oral and intravenous administration of cefdinir

A selective and sensitive liquid chromatography tandem mass spectrometry method (LC‐MS/MS) was developed and validated for the determination of cefdinir in rat plasma and urine. Following a simple protein precipitation using methanol, chromatographic separation was achieved with a run time of 10 min using a Synergi 4 µ polar‐RP 80A column (150 × 2.0 mm, 4 µm) with a mobile phase consisting of 0.1% formic acid in water and methanol (65:35, v/v) at a flow rate of 0.2 mL/min. The protonated precursor and product ion transitions for cefdinir (m/z 396.1 → 227.2) and cefadroxil, an internal standard (m/z 364.2 → 208.0) were monitored in the multiple reaction monitoring in positive ion mode. The calibration curves for plasma and urine were linear over the concentration range 10–10,000 ng/mL. The lower limit of quantification was 10 ng/mL. All accuracy values were between 95.1 and 113.0% and the intra‐ and inter‐day precisions were <13.0% relative standard deviation. The stability under various conditions in rat plasma and urine was also found to be acceptable at three concentrations. The developed method was applied successfully to the pharmacokinetic study of cefdinir after oral and intravenous administration. Copyright © 2013 John Wiley & Sons, Ltd.