ANALYTICA CHIMICA ACTA
·
2026
·
IF 6.1
Dong Wang,Mengrong Li,Xiangyu Zhang,Xu Miao,Lifeng Han,Di Chen
Background Therapeutic drug monitoring (TDM) of tyrosine kinase inhibitors (TKIs) is essential for individualized dosing due to their narrow therapeutic windows and pronounced pharmacokinetic variability. However, routine TDM is still hindered by sample preparation strategies that rely on labor-intensive workflows, high consumption of toxic organic solvents, and poor procedural standardization, limiting their suitability for high-throughput and green clinical analysis. Therefore, there is a clear need for a standardized, eco-friendly, and ready-to-use sample preparation strategy that enables robust and routine determination of TKIs in plasma. Results Herein, a standardized, ready-to-use extraction device inspired by pharmaceutical blister packaging was developed for the determination of nine TKIs in human plasma. Hydrophobic natural deep eutectic solvent (NADES, menthol–thymol, 2:1) was pre-impregnated into polypropylene fiber (PPF) and sealed as individual consumable units, enabling a unit-supported liquid-phase microextraction (NADES-PPF-SLPME) strategy suitable for high-throughput operation. Density functional theory revealed that extraction was governed by synergistic hydrogen bonding and π–π stacking interactions between NADES and TKIs. Under Box–Behnken optimized conditions, the method exhibited wide linearity (R 2 ≥ 0.990), low limits of quantification (0.2–1.0 ng/mL), satisfactory recoveries (86.64–110.30%), and acceptable precision (RSD < 14.10%). The standardized units retained extraction capacity above 86.47% after three months of storage and enabled reliable quantification of TKIs in real clinical plasma samples. Significance This work introduces a robust “prepare-in-advance, use-on-demand” NADES-based microextraction strategy that integrates standardization, operational robustness, high throughput, and green analytical chemistry. By eliminating on-site solvent preparation and minimizing solvent consumption, the proposed method offers an eco-friendly and operationally simple solution for routine clinical TDM of TKIs in plasma.
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Journal of Mass Spectrometry and Advances in the Clinical Lab
·
2023
·
IF 2.2
Fangjun Chen,Wenda Chen,Zhenxin Wang,Yingfei Peng,Beili Wang,Baishen Pan,Wei Guo
Introduction Tyrosine kinase inhibitors (TKIs) are widely used in tumor treatment. The detection of these medicines by liquid chromatography-tandem mass spectrometry (LC-MS/MS) can avoid the interference of structurally similar compounds. Objectives This study aimed to develop and validate a new LC-MS/MS assay for the quantification of eight tyrosine kinase inhibitors in human plasma and to preliminarily evaluate the clinical utility of the therapeutic drug monitoring method. Methods Plasma samples were prepared by simple protein precipitation and separated using an ultra-high-performance reversed phase column. Detection was achieved using a triple quadrupole mass spectrometer in the positive ionization mode. The assay was validated against standard guidelines. We reviewed and analyzed the results of 268 plasma samples obtained from patients administered imatinib and other TKIs collected from January 2020 to November 2021 at Zhongshan Hospital. The analytes were separated and quantified within 3.5 min. Results The newly developed method demonstrated linearity for the detected drug concentration in the range of 20 to 2000 ng/ml for gefitinib (r 2 = 0.991) and crizotinib (r 2 = 0.992), 50 to 5000 ng/ml for nilotinib (r 2 = 0.991) and imatinib (r 2 = 0.995), 1500–150,000 ng/ml for vemurafenib (r 2 = 0.998), 1000–100,000 ng/ml for pazopanib (r 2 = 0.993), 0.5–100 ng/ml for axitinib (r 2 = 0.992) and 5–500 ng/ml for sunitinib (r 2 = 0.991) and N-desethyl sunitinib (r 2 = 0.998). The lower limit of quantification (LLOQ) was 20 ng/ml for gefitinib and crizotinib, 50 ng/ml for nilotinib and imatinib, 1500 ng/ml for vemurafenib, 1000 ng/ml for pazopanib, 0.5, and 5 ng/ml for sunitinib and N-desethyl sunitinib, respectively. Specificity, precision, accuracy, and stability were tested, and met the requirements of the guidelines. At the same dose, there was no significant difference in plasma drug concentration between the original imatinib medicine and the generic medicine after patent expiration. Conclusion We developed a sensitive and reliable method for the quantification of eight TKIs.
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ANALYTICA CHIMICA ACTA
·
2024
·
IF 5.7
Jing Ye,Yuanyuan Zheng,Xiangyu Li,Xingyi Jiang,Di Chen
Background The detection of tyrosine kinase inhibitors (TKIs) in biological fluids is essential due to their critical role in cancer therapy and the variability in individual drug metabolism, which necessitates precise dosing. Traditional methods for analyzing TKIs in biological fluids, such as blood plasma, typically involve complex sample preparation techniques that can be resource-intensive, environmentally burdensome, and not sufficiently sensitive for low-concentration analytes. There is a pressing need for more efficient, economical, and environmentally friendly methods that can enhance sensitivity and throughput without compromising accuracy. Results This study explores the use of melt-blown polypropylene nonwoven (MBPP), commonly found in face masks, as a novel sorbent for pipette-tip micro-solid phase extraction (PT-μSPE). MBPP demonstrated excellent hydrophobicity and significant mesoporous adsorption capacity. An extraction device was fashioned by inserting a segment of MBPP (15 mg) into a 200 μL disposable plastic pipette tip, which was then attached to a 2.5 mL disposable plastic syringe. The MBPP's fabric form removes the need for a frit, allowing the extraction process to be completed in just 3 min through simple plunger manipulation. The method achieved extraction recoveries ranging from 60.5 % to nearly 100 %. Subsequent method validation using liquid chromatography-tandem mass spectrometry (LC-MS/MS) showed satisfactory linearity (coefficient of determination R 2 > 0.993), accuracy (relative recoveries: 86.3%–114.8 %), and precision (relative standard deviation: 3.4%–11.3 %), with detection limits between 0.022 and 0.135 ng mL −1 . Significance The introduction of MBPP for PT-μSPE represents a significant advancement in the bioanalytical detection of TKIs, offering a highly efficient, cost-effective, and environmentally sustainable method. It compares favorably with existing techniques, offering advantages in terms of cost, environmental impact, and ease of use. This approach has the potential to be widely adopted for routine monitoring of TKIs in clinical settings.
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Arabian Journal of Chemistry
·
2024
·
IF 5.3
Qianqian Wang,Yuwei Liu,Yuanyuan Zheng,Di Chen,Ya Xie,Nian Shi
This work presents an advanced automated monolithic C18 pipette-tip solid-phase extraction (PT-SPE) method seamlessly integrated with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for precise therapeutic drug monitoring of eleven tyrosine kinase inhibitors (TKIs) in biological samples. Commercially available MonoTip C18 columns facilitate superior extraction efficiency and selectivity from complex biological matrices owing to their large surface areas and enhanced mass transfer capabilities. The sample preparation process, conducted by aspirating and dispensing solutions using a pipettor, completes the overall extraction process within 3 min. The method validation demonstrated excellent linearity within the range of 0.2/0.5/0.8 to 200 ng/mL, with detection limits ranging from 0.049 to 0.206 ng/mL. The method exhibited outstanding accuracy and precision, with intraday relative recovery rates ranging from 96.3 % to 115.0 % and interday recovery rates ranging from 95.0 % to 115.7 %, with coefficient of variation values consistently below 13.8 %. The proposed method is distinguished by its exceptional efficiency, reduced solvent use, enhanced environmental sustainability, and streamlined automation—key advantages in the realm of clinical therapeutic drug monitoring of TKIs. Overall, the MonoTip C18 PT-SPE technique, coupled with LC-MS/MS, offers a formidable, eco-friendly, and effective strategy for the TDM of TKIs, marking a significant advancement in the field.
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JOURNAL OF CHROMATOGRAPHY A
·
2024
·
IF 3.8
Qianqian Wang,Yuanyuan Zheng,Bowen Deng,Di Chen,Liuqun Jia,Nian Shi
This study delineates the development of a novel automated pipette-tip solid-phase extraction (SPE) methodology, employing kapok fiber as a naturally efficient and cost-effective adsorbent for the selective extraction of eleven tyrosine kinase inhibitors (TKIs) from plasma. The uniqueness of this method lies in its assembly, where kapok fibers are ingeniously wrapped around a stainless-steel spring within the pipette tip, ensuring an obstruction-free central space for effortless solution aspiration and dispensation. This design significantly minimizes backpressure, enhancing operational efficiency and ensuring compatibility with pipettors, including the implementation of an electric pipettor to streamline the sample preparation process and facilitate automation. The method's analytical performance, rigorously validated through liquid chromatography-tandem mass spectrometry, exhibits outstanding linearity in ranges of 0.1/0.5–200 ng mL -1 (R² > 0.993), commendable accuracy (86.3%–114.8%), and consistent precision (3.4–11.3%), alongside remarkably low detection limits that span from 0.024 to 0.130 ng mL -1 . The assembly of kapok fiber within the pipette tip, in this unique configuration, results in a practical, cost-effective, eco-friendly, and automated pipette-tip SPE method. This innovation signifies a significant advancement in bioanalytical methodologies, offering an efficient and sustainable approach for extracting analytes from complex biological samples. This process notably enhances both the sensitivity and selectivity of subsequent instrumental analyses.
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JOURNAL OF CHROMATOGRAPHY A
·
2025
·
IF 4
Dong Wang,Mengrong Li,Tingting Dai,Xiangyu Zhang,Di Chen
Accurate quantification of tyrosine kinase inhibitors (TKIs) in plasma is essential for therapeutic drug monitoring (TDM). This study presents a novel solid phase extraction (SPE) method employing hydrophobic polypropylene fabric (PPF)—a fibrous material derived from oil-absorbent pads—as the sorbent. The PPF-SPE device was prepared by directly packing fluffed PPF into syringe barrels, eliminating the need for sieve plates and simplifying column assembly. Integrated with liquid chromatography-tandem mass spectrometry (LC-MS/MS), the method enabled sensitive determination of eight clinically relevant TKIs (afatinib, alectinib, ceritinib, dasatinib, sunitinib, pazopanib, tamoxifen, and ibrutinib) in plasma. Key parameters, including PPF amount, sample pH, and desorption conditions, were systematically optimized, yielding high extraction recoveries (83.1–96.4 %) and good reproducibility (RSDs<5.5 %). The method showed excellent linearity (R²>0.99), low detection limits (0.017–0.055 ng/mL), and high intra-/inter-day recoveries (85.1 %–102.6 %) and precision (RSDs<5.3 %). Its practical applicability was validated in spiked plasma under a single-blind design, yielding relative errors of –8.2 % to 5.4 %. Compared to traditional SPE methods, PPF-SPE offers significant advantages in operational simplicity, cost-effectiveness, high throughput, and environmental sustainability.
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RSC Advances
·
2025
·Vol. 15
·期 40
·33536-33548
·
IF 4.6
Xiaofei Zhang,Mengyuan Lv,Yuyang Wang,Nan Zhang,Di Chen
Tyrosine kinase inhibitors (TKIs) are critical in cancer therapy, but their clinical application is complicated by narrow therapeutic windows and significant interpatient variability in pharmacokinetics. To address this, this study presents an effective pipette-tip solid-phase microextraction (PT-μSPE) method using kapok fiber-derived biochar (KFB) as a green and cost-effective sorbent for the extraction of TKIs in plasma. The KFB was incorporated as an inner-wall coating within a standard pipette tip, minimizing backpressure and enhancing automation compatibility. This PT-μSPE method is optimized for efficiency and sensitivity, with ethanol used as the desorption solvent. The method is coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the determination of TKIs, demonstrating excellent linearity (R2 > 0.99), sensitivity (LOD: 0.022–0.125 ng mL−1), and reproducibility. Furthermore, the method exhibits notable green chemistry characteristics, including minimal solvent usage and environmental sustainability. The proposed method offers a practical, scalable solution for TKI quantification for potential clinical and pharmacokinetic studies, with potential for high-throughput integration into automated systems.
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