Analytical validation and clinical application of urinary vanillylmandelic acid and homovanillic acid by LC–MS/MS for diagnosis of neuroblastoma

Vanillylmandelic acid (VMA) and homovanillic acid (HVA) are clinical biomarkers for diagnosis of neuroblastoma (NB), which commonly occurs in the childhood. Development and application of a robust LC–MS/MS method for fast determination of these biomarkers for optimal laboratory testing of NB is essential in clinical laboratories. In present study, we developed and validated a simple liquid chromatography tandem mass spectrometry (LC–MS/MS) method for quick clinical testing of VMA and HVA for diagnosis of NB. The method was validated according to the current CLSI C62‐A and FDA guidelines. The age‐adjusted pediatric reference intervals and diagnostic performance were evaluated in both 24 h urine and random urine. Injection‐to‐injection time was 3.5 min. Inter‐ and intra‐assay coefficients of variation (CVs) were ≤3.88%. The lower limit of quantification and the limit of detection were 0.50 and 0.25 μmol/L for both VMA and HVA. Recoveries of VMA and HVA were in the ranges of 85–109% and 86–100% with CVs ≤5.76%. This method was free from significant matrix effect, carryover and interference. The establishment of age‐adjusted pediatric reference intervals by this LC–MS/MS method was favorable for the improvement in diagnostic performance, which was crucial for correct interpretation of test results from children in both 24 h and random urine.     

GC–MS/MS method for the determination and pharmacokinetic analysis of borneol and muscone in rat after the intravenous administration of Xingnaojing injection

A simple and sensitive gas chromatography with tandem mass spectrometry method was developed and validated for the simultaneous determination of borneol and muscone in rat plasma. The analytes and internal standard, naphthalene, were extracted using a convenient one‐step liquid–liquid extraction method with ethyl acetate. The chromatographic separation was realized on a HP‐5MS capillary column and detected in multiple reaction monitoring mode. Excellent linearity (R ² ≥ 0.996) was shown over 10.0–5000 ng/mL for borneol and 2.5–250 ng/mL for muscone. The lower limit of quantitation was 10 and 2.5 ng/mL for borneol and muscone, respectively. The intra‐ and interday precisions were less than 7.52%, and the accuracy values were between  −8.03 and 14.52%. The extraction recovery, matrix effect, and stability were sufficient to meet the Food and Drug Administration criteria. Meanwhile, the assay was successfully applied to the preclinical pharmacokinetic study of borneol and muscone following intravenous administration of Xingnaojing injection, a modern Chinese herbal medicine preparation.     

Development of a solid‐phase microextraction LC–MS/MS method for determination of oxidative stress biomarkers in biofluids

Recently the connection between oxidative stress and various diseases, including cancer and Alzheimer's, attracts notice as a pathway suitable for diagnostic purposes. 8‐Oxo‐deoxyguanosine and 8‐oxo‐deoxyadenosine produced from the interaction of reactive oxygen species with DNA become prominent as biomarkers. Several methods have been developed for their determination in biofluids, including solid‐phase extraction and enzyme‐linked immunosorbent assays. However, still, there is a need for reliable and fast analytical methods. In this context, solid‐phase microextraction offers many advantages such as flexibility in geometry and applicable sample volume, as well as high adaptability to high‐throughput sampling. In this study, a solid‐phase microextraction method was developed for the determination of 8‐oxo‐deoxyguanosine and 8‐oxo‐deoxyadenosine in biofluids. The extractive phase of solid‐phase microextraction consisted of hydrophilic–lipophilic balanced polymeric particles. In order to develop a solid‐phase microextraction method suitable for the determination of the analytes in saliva and urine, several parameters, including desorption solvent, desorption time, sample pH, and ionic strength, were scrutinized. Analytical figures of merit indicated that the developed method provides reasonable interday and intraday precisions (<15% in both biofluids) with acceptable accuracy. The method provides a limit of quantification for both biomarkers at 5.0 and 10.0 ng/mL levels in saliva and urine matrices, respectively.     

Development of a novel HPLC‐MS/MS method for the determination of aconitine and its application to in vitro and rat microdialysis samples

A sensitive and selective LC‐MS/MS method was developed and validated for the determination of aconitine in microdialysate and rat plasma. Extraction of plasma sample was conducted by use of 1% trichloracetic acid and acetonitrile solution with 10 ng/mL internal standard (propafenone) spiked. Microdialysates were analyzed without sample purification. After sample preparation, 2 µL were injected and separated with an isocratic mobile phase consisting of acetonitrile:0.1% formic acid (60:40, v/v) at a flow rate of 0.3 mL/min. The Agilent G6410A triple quadrupole LC/MS system was operated under the multiple‐reaction monitoring mode (MRM) using the electrospray ionization technique in positive mode. Overall, the assay exhibited good precision and accuracy. The diffusion properties of aconitine investigated in in vitro microdialysis experiments revealed unfavourable concentration dependence avertable by keeping a constant pH 5.77 using isotonic phosphate buffer solution as perfusate. The mean relative recoveries were 48.23% [coefficient of variation (CV 4.47%)] and 55.38% (CV 2.89%) for retrodialysis and recovery experiments, respectively. The in vivo recovery of aconitine was 34.48% (CV 3.05%) and was stable over the 6 h study period. Following characterization of aconitine both in vitro and in vivo microdialysis, the developed setting is suitable for application in pharmacokinetics and pharmacodynamics studies. Copyright © 2009 John Wiley & Sons, Ltd.     

Development and validation of a highly sensitive and robust LC‐ESI‐MS/MS method for simultaneous quantitation of simvastatin acid,amlodipine and valsartan in human plasma: application to a clinical pharmacokinetic study

A high‐throughput, simple, highly sensitive and specific LC‐MS/MS method has been developed for simultaneous estimation of simvastatin acid (SA), amlodipine (AD) and valsartan (VS) with 500 µL of human plasma using deuterated simvastatin acid as an internal standard (IS). The API‐4000 LC‐MS/MS was operated under the multiple reaction‐monitoring mode (MRM) using electrospray ionization. The assay procedure involved precipitation of SA, AD, VS and IS from plasma with acetonitrile. The total run time was 2.8 min and the elution of SA, AD, VS and IS occurred at 1.81, 1.12, 1.14 and 1.81 min, respectively; this was achieved with a mobile phase consisting of 0.02 m ammonium formate (pH 4.5):acetonitrile (20:80, v/v) at a flow rate of 0.50 mL/min on an X‐Terra C₁₈ column. A linear response function was established for the range of concentrations 0.5–50 ng/mL (r > 0.994) for VS and 0.2–50 ng/mL (r > 0.996) for SA and AD. The method validation parameters for all three analytes met the acceptance as per FDA guidelines. This novel method has been applied to human pharmacokinetic study. Copyright © 2009 John Wiley & Sons, Ltd.     

Automated determination of venlafaxine in human plasma by on‐line SPE‐LC‐MS/MS. Application to a bioequivalence study

A new automated SPE‐LC‐ESI‐MS/MS method was developed and validated to quantify venlafaxine in human plasma using fluoxetine as an internal standard. The analytes were automatically extracted from plasma by C18 SPE cartridges, separated on a C8 RP column and analyzed by MS in the multiple reaction‐monitoring (MRM) mode. The method has a chromatographic run time of 4.0 min and a linear calibration curve over the range of 0.25–200 ng/mL (r >0.997). The between‐run precisions, based on the percent RSD for replicate quality controls (0.75; 80, and 200 ng/mL), were < 8.5% for all concentrations. The between‐run accuracies, based on the percent relative error, were < 4.0%. This method was successfully employed in a bioequivalence study of two venlafaxine capsule formulations (test formulation from Eurofarma (Brazil) and Efexor XR, reference formulation, from Wyeth‐Whitehall, Brazil) in 48 healthy volunteers of both sexes who received a single 150 mg dose of each formulation. More than 3000 samples were analyzed eliminating the analyst's exposure to hazardous organic solvents normally employed in off‐line liquid–liquid extractions. The 90% confidence interval (CI) of the individual ratio geometric mean for Test/Reference was 91.6–103.4% for AUC_{0–48 h} and 102.2–112.6% for C_max. Since both 90% CI for AUC_{0–48 h} and C_max were included in the 80–125% interval proposed by the US Food and Drug Administration (FDA) and the Brazilian National Health Surveillance Agency (ANVISA), the test formulation was considered bioequivalent to Efexor XR according to both the rate and extent of absorption.     

Assay of free captopril in human plasma as monobromobimane derivative,using RPLC/(+)ESI/MS/MS: validation aspects and bioequivalence evaluation

A sensitive method for determination of free captopril as monobromobimane derivative in plasma samples is discussed. The internal standard (IS) was 5‐methoxy‐1H‐benzimidazole‐2‐thiol. Derivatization with monobromobimane immediately after blood collection and plasma preparation prevents oxidation of captopril to the corresponding disulfide compound and enhances the ionization yield. Consequently, derivatization enhances sample stability and detection sensitivity. Addition of the internal standard was made immediately after plasma preparation. The internal standard was also derivatized by monobromobimane, as it contains a thiol functional group. Preparation of plasma samples containing captopril and IS derivatives was based upon protein precipitation through addition of acetonitrile, in a volumetric ratio 1:2. The reversed‐phase liquid chromatographic separation was achieved on a rapid resolution cartridge Zorbax SB‐C₁₈, monitored through positive electrospray ionization and tandem MS detection using the multiple‐reaction monitoring mode. Transitions were 408–362 amu for the captopril derivative and 371–260 amu for the internal standard derivative. The kinetics of captopril oxidation to the corresponding disulfide compound in plasma matrix was also studied using the proposed method. A linear log–log calibration was obtained over the concentration interval 2.5–750 ng/mL. A low limit of quantitation in the 2.5 ng/mL range was obtained. The analytical method was fully validated and successfully applied in a three‐way, three‐period, single‐dose (50 mg), block‐randomized bioequivalence study for two pharmaceutical formulations (captopril LPH 25 and 50 mg) against the comparator Capoten 50 mg. Copyright © 2009 John Wiley & Sons, Ltd.     

Rapid quantification of levosulpiride in human plasma using RP‐HPLC‐MS/MS for pharmacokinetic and bioequivalence study

A rapid and validated method for analysis of levosulpiride in human plasma using liquid chromatography coupled to tandem mass spectrometry was developed. Levosulpiride and tiapride (IS, internal standard) were extracted from alkalized plasma samples with ethylacetate and separation by RP‐HPLC. Detection was performed by positive ion electrospray ionization in multiple‐reaction monitoring mode, monitoring the transitions m/z 342.1 → m/z 112.2 and m/z 329.1 → m/z 213.2, for quantification of levosulpiride and IS, respectively. The standard calibration curves showed good linearity within the range of 2–200 ng/mL (r² ≥ 0.9990). The lower limit of quantitation was 2 ng/mL. The retention times of levosulpiride (0.63 min) and IS (0.66 min) presented a significant time saving benefit of the proposed method. No significant metabolic compounds were found to interfere with the analysis. This method offered good precision and accuracy and was successfully applied for the pharmacokinetic and bioequivalence study of a 25 mg of levosulpiride tablet in 24 healthy Korean volunteers. Copyright © 2009 John Wiley & Sons, Ltd.     

A validated LC‐MS/MS method for the determination of senkyunolide I in dog plasma and its application to a pharmacokinetic and bioavailability studies

Senkyunolide I is one of the major bioactive components in the herbal medicine Ligusticum chuanxiong. The aim of this study was to develop and validate a fast, simple and sensitive LC‐MS/MS method for the determination of senkyunolide I in dog plasma. The plasma samples were processed with acetonitrile and separated on a Waters Acquity UPLC BEH C₁₈ column (50 × 2.1 mm, 1.7 μm). The mobile phase consisted of 0.1% formic acid aqueous and acetonitrile was delivered at a flow rate of 0.3 mL min⁻¹. The detection was achieved in the positive selected reaction monitoring mode with precursor‐to‐product transitions at m/z 225.1 → 161.1 for senkyunolide I and at m/z 349.1 → 305.1 for an internal standard. The assay was linear over the tested concentration range, from 0.5 ng mL⁻¹ to 1000 ng mL⁻¹, with a correlation coefficient >0.9992. The mean extraction recovery from dog plasma was within the range of 85.78–93.25%, while the matrix effect of the analyte was within the range of 98.23–108.89%. The intra‐ and inter‐day precisions (RSD) were <12.12% and the accuracy (RR) ranged from 98.89% to 104.24%. The validated assay was successfully applied to pharmacokinetic and bioavailability studies of senkyunolide I in dogs. The results demonstrated that (a) senkyunolide I showed short elimination half‐life (<1 h) in dog, (b) its oral bioavailability was >40% and (c) senkyunolide I showed dose‐independent pharmacokinetic profiles in dog plasma over the dose range of 1–50 mg kg⁻¹.     

Simultaneous analysis of multiple urinary biomarkers for the evaluation of oxidative stress by automated online in‐tube solid‐phase microextraction coupled with negative/positive ion‐switching mode liquid chromatography–tandem mass spectrometry

This study described an automated online method for the simultaneous determination of 8‐isoprostane, 8‐hydroxy‐2′‐deoxyguanosine, and 3‐nitro‐l ‐tyrosine in human urine. The method involves in‐tube solid‐phase microextraction using a Carboxen 1006 PLOT capillary column as an extraction device, followed by liquid chromatography with tandem mass spectrometry using a CX column and detection in the negative/positive switching ion‐mode by multiple reaction monitoring. Using their stable isotope‐labeled internal standards, each of these oxidative stress biomarkers showed good linearity from 0.02 to 2.0 ng/mL. Their detection limits (S/N = 3) were 3.4–21.5 pg/mL, and their intra‐ and inter‐day precisions (relative standard deviations) were >3.9 and 6.5% (n = 5), respectively. This method was applied successfully to the analysis of urine samples, without any other pretreatment and interference peaks.     

Development of an LC‐MS/MS method for quantification of kadsurenone in rat plasma and its application to a pharmacokinetic study

A sensitive and rapid LC‐MS/MS method was developed and validated for the determination of kadsurenone in rat plasma using lysionotin as the internal standard (IS). The analytes were extracted from rat plasma with acetonitrile and separated on a SB‐C₁₈ column (50 × 2.1 mm, i.d.; 1.8 µm) at 30 °C. Elution was achieved with a mobile phase consisting of methanol–water–formic acid (65:35:0.1, v/v/v) at a flow rate of 0.30 mL/min. Detection and quantification for analytes were performed by mass spectrometry in the multiple reaction monitoring mode with positive electrospray ionization m/z at 357.1 → 178.1 for kadsurenone, and m/z 345.1 → 315.1 for IS. Calibration curves were linear over a concentration range of 4.88–1464 ng/mL with a lower limit of quantification of 4.88 ng/mL. The intra‐ and inter‐day accuracies and precisions were <8.9%. The LC‐MS/MS assay was successfully applied for oral pharmacokinetic evaluation of kadsurenone using the rat as an animal model. Copyright © 2013 John Wiley & Sons, Ltd.     

Determination of MLN0128, an investigational antineoplastic agent,in human plasma by LC–MS/MS

MLN0128, an mTOR kinase inhibitor, is currently undergoing clinical investigation for treatment of a variety of cancers. To support this work, an LC–MS/MS method has been developed for the determination of MLN0128 in human plasma. A structural analog STK040263 was used as the internal standard. Both MLN0128 and the IS were first extracted from plasma using methyl tert ‐butyl ether; then separated on a Waters XTerra® MS C₁₈ column using a mobile phase consisting of methanol–acetonitrile–10.0 mm ammonium formate (34:6:60, v /v/v) at a flow rate of 0.300 mL min⁻¹. Quantitation of MLN0128 was done by positive electrospray ionization tandem mass spectrometry in multiple‐reaction‐monitoring mode. This method has a total run time of <4 min with the retention times of 1.95 and 2.94 min for the IS and MLN0128, respectively. The method has been validated per the US Food and Drug Administration guidance for bioanalytical method validation. It has a calibration range of 0.100–50.0 ng mL⁻¹ in human plasma with a correlation coefficient > 0.999. The overall assay accuracy and precision were ≤ ± 4 and ≤8%, respectively. The IS normalized recovery of MLN0128 was 98–100%. The stability studies showed that MLN0128 was stable under all tested conditions. The method developed may be useful for clinical studies of MLN0128.     

On‐line 2D‐LC‐ESI/MS/MS determination of rifaximin in rat serum

A highly sensitive and selective on‐line two‐dimensional reversed‐phase liquid chromatography/electrospray ionization–tandem mass spectrometry (2D‐LC‐ESI/MS/MS) method was developed and validated to determine rifaximin in rat serum by direct injection. The 2D‐LC‐ESI/MS/MS system consisted of a restricted access media column for trapping proteins as the first dimension and a Waters C₁₈ column as second dimension using 0.1% aqueous acetic acid:acetonitrile as mobile phase in a gradient elution mode. Rifampacin was used as an internal standard. The linear dynamic range was 0.5–10 ng/mL (r² > 0.998). Acceptable precision and accuracy were obtained over the calibration range. The assay was successfully used in analysis of rat serum to support pharmacokinetic studies. Copyright © 2009 John Wiley & Sons, Ltd.     

Liquid-liquid extraction coupled with LC/MS/MS for monitoring of malonyl-CoA in rat brain tissue

The formation of malonyl-CoA is catalyzed by acetyl-CoA carboxylase (ACC), the rate-limiting enzyme of de novo fatty acid synthesis. Monitoring the changes of malonyl-CoA concentration in the brain in response to treatments such as pharmaceutical intervention (via ACC inhibitors) or different dietary conditions (such as varied feeding regimes) is of great interest and could help increase the understanding of how this molecule contributes to feeding behavior and overall energy balance. We have developed a sensitive analytical method for the determination of malonyl-CoA levels in rat brain tissue. The assay involved removal of tissue lipids by liquid-liquid extraction followed by LC/MS/MS analysis of the aqueous layer for malonyl-CoA. The method was sensitive enough (limit of quantitation = 50 ng/mL, or approximately 0.018 nmol/g brain tissue) to determine malonyl-CoA in individual rat brain preparations. The assay performance was sufficiently rugged to support drug discovery screening efforts and provided an additional analytical tool for monitoring brain malonyl-CoA levels.     

Targeted metabolomic analysis of 33 amino acids and biogenic amines in human urine by ion‐pairing HPLC‐MS/MS: Biomarkers for tacrolimus nephrotoxicity after renal transplantation

Calcineurin inhibitor nephrotoxicity, especially for the widely used tacrolimus, has become a major concern in post‐transplant immunosuppression. Multiparametric amino acid metabolomics is useful for biomarker identification of tacrolimus nephrotoxicity, for which specific quantitative methods are highlighted as a premise. This article presents a targeted metabolomic assay to quantify 33 amino acids and biogenic amines in human urine by high‐performance liquid chromatography coupled with tandem mass spectrometry. Chromatographic separation was carried out on an Agilent Zorbax SB‐C₁₈ column (3.0 × 150 mm, 5 μm) with addition of an ion‐pairing agent in the mobile phase, and MS/MS detection was achieved in both the positive and negative multiple reaction monitoring modes. Good correlation coefficients (r² > 0.98) were obtained for most analytes. Intra‐ and inter‐day precision, stability, carryover and incurred sample reanalysis met with the acceptance criteria of the guidance of the US Food and Drug Administration. Analysis on urine from healthy volunteers and renal transplantation patients with tacrolimus nephrotoxicity confirmed symmetric dimethylarginine and serine as biomarkers for kidney injury, with AUC values of 0.95 and 0.81 in receiver operating characteristic analysis, respectively. Additionally, symmetric dimethylarginine exhibited a tight correlation with serum creatinine, and was therefore indicative of renal function. The targeted metabolomic assay was time and cost prohibitive for amino acid analysis in human urine, facilitating the biomarker identification of tacrolimus nephrotoxicity.     

A robust LC–MS/MS assay with online cleanup for measurement of serum testosterone

Accurate measurement of low levels of testosterone is critical for diagnosis and treatment of androgen disorders. The very low concentrations of testosterone in children, females, and males with androgen suppression therapies necessitate the use of mass spectrometry‐based methods. We aimed to develop a liquid chromatography with tandem mass spectrometry method with simplified sample preparation and online solid‐phase extraction cleanup to achieve enhanced precision, accuracy, robustness, and cost‐effectiveness. The assay was linear from 10 to 20 000 pg/mL with an analytical recovery of 93–104%. The total coefficient of variation was 2.5, 1.9, and 1.7% at concentration levels of 348, 5432, and 10 848 pg/mL, respectively. No significant carryover was observed from samples with concentrations up to 20 000 pg/mL. No significant interference was observed from androstenedione, dehydroepiandrosterone, epi‐testosterone, and estriol. Comparison with CDC Hormone Standardization program (HoSt) reference samples with defined values (n = 40) showed a Deming regression slope of 0.963, intercept of 28.06 pg/mL, standard error of estimate was 66.9, a correlation coefficient of 0.9996, and a mean bias of ?0.6%. The method met the accuracy criteria by the CDC HoSt program. In addition, we achieved >12 000 injections on a single analytical column without significant performance deterioration due to the specific online solid‐phase extraction settings.     

High‐throughput LC–MS/MS method with 96‐well plate precipitation for the determination of arotinolol and amlodipine in a small volume of rat plasma: Application to a pharmacokinetic interaction study

A rapid, sensitive, and selective liquid chromatography with tandem mass spectrometry method was developed and fully validated for the simultaneous quantification of arotinolol and amlodipine in rat plasma. Two internal standards were introduced with metoprolol as the internal standard of arotinolol and (S)‐amlodipine‐d4 as the internal standard of amlodipine. The analytes were isolated from 50.0 μL plasma samples by a simple protein precipitation using acetonitrile. The chromatographic separation was achieved in 5 min on a C18 column. The mobile phase consisted of phase A 5% methanol and phase B 95% methanol (both containing 0.5% formic acid and 5 mM ammonium acetate) and was delivered in gradient elution at 0.300 mL/min. Quantification was performed in multiple reaction monitoring mode with the transition m/z 372.1 → 316.1 for arotinolol, m/z 268.2 → 116.2 for metoprolol, m/z 409.1 → 238.1 for amlodipine and m/z 413.1 → 238.1 for (S)‐amlodipine‐d4. Linearity was obtained over the range of 0.200–40.0 ng/mL for arotinolol (r² = 0.9988) and 0.500–100 ng/mL for amlodipine (r² = 0.9985) in rat plasma. The validated data have met the acceptance criteria in FDA guideline. This method was successfully applied to a pharmacokinetic interaction study in rats, and the results indicated that there was no significant drug–drug interaction between arotinolol and amlodipine.     

Development and validation of a sensitive assay for the quantification of imatinib using LC/LC‐MS/MS in human whole blood and cell culture

We developed and validated a semi‐automated LC/LC‐MS/MS assay for the quantification of imatinib in human whole blood and leukemia cells. After protein precipitation, samples were injected into the HPLC system and trapped onto the enrichment column (flow 5 mL/min); extracts were back‐flushed onto the analytical column. Ion transitions [M + H]⁺ of imatinib (m/z = 494.3 → 394.3) and its internal standard trazodone (372.5 → 176.3) were monitored. The range of reliable response was 0.03–75 ng/mL. The inter‐day precisions were: 8.4% (0.03 ng/mL), 7.2% (0.1 ng/mL), 6.5% (1 ng/mL), 8.2% (10 ng/mL) and 4.3% (75 ng/mL) with no interference from ion suppression. Autosampler stability was 24 hs and samples were stable over three freeze–thaw cycles. This semi‐automated method is simple with only one manual step, uses a commercially available internal standard, and has proven to be robust in larger studies. Copyright © 2009 John Wiley & Sons, Ltd.     

Syringe cleanup with UHPLC–MS/MS for nitroimidazoles and steroids detection in manure‐based fertilizers

A syringe‐dispersive solid‐phase extraction method was developed for the determination of seven nitroimidazoles and nine steroids in manure‐based fertilizers by ultra‐high performance liquid chromatography with tandem mass spectrometry. Methanol and acetonitrile were used to extract the sample, and mixed dispersive sorbents dispersed in the syringe were used for purification. The extract was separated with an HSS‐T3 column and detected in positive or negative multiple reaction monitoring mode. Under the optimal conditions, the recoveries of the 16 compounds ranged from 70.3 to 112.3% at the four spiked levels (3, 10, 20, and 50 μg/kg) and the relative standard deviations ranged from 1.0 to 12.4%. The limits of detection and quantification were 0.22–0.86 and 0.73–2.87 μg/kg, respectively. This method is simple, fast, and reliable, and can be used to simultaneously screen and determine nitroimidazoles and steroids in manure‐based fertilizers.     

Performance comparison of dispersive solid‐phase extraction and multiplug filtration cleanup methods for the determination of tefuryltrione in plant and environmental samples using UHPLC–MS/MS

The detection frequencies of tefuryltrione, a new type of 4‐hydroxyphenyl‐pyruvate dioxygenase inhibitor herbicide, are rarely reported, probably because of the paucity of analytical methods. Herein, an effective and sensitive analytical method has been developed to detect tefuryltrione in vegetables (tomato and cucumber), cereals (rice and corn), soil, and water by ultra high performance liquid chromatography coupled with tandem mass spectrometry. Comparisons of the performances of dispersive solid‐phase extraction and multiplug filtration cleanup methods were carried out for tefuryltrione in complex matrices. Extraction solvents and purification sorbents were further optimized for dispersive solid‐phase extraction. Tefuryltrione was analyzed with electrospray ionization in the positive mode within 2.0 min. Mean recoveries for tefuryltrione were 75.4–108.9% with relative standard deviations less than 11.0% at three fortification levels (10, 100, 500 μg/kg) in the sample matrixes. Limits of quantification ranged from 0.70 to 5.12 μg/kg, and an excellent linearity (R ² ≥ 0.9902) was obtained for tefuryltrione at concentrations of 5–1000 μg/L. The results showed that the developed dispersive solid‐phase extraction method could serve as an effective, sensitive, and robust method for routine monitoring of tefuryltrione residue in plants and environmental samples.