A new high-performance liquid chromatography–tandem mass spectrometry method for the determination of sunitinib and N-desethyl sunitinib in human plasma: Light-induced isomerism overtaking towards therapeutic drug monitoring in clinical routine

Marangon, Elena; Buzzo, Mauro; Posocco, Bianca; Gagno, Sara; Zanchetta, Martina; Iacuzzi, Valentina; Poetto, Ariana Soledad; Guardascione, Michela; Giodini, Luciana; Toffoli, Giuseppe

doi:10.1016/j.jpba.2019.112949

Cited by 10 publications

(8 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, there is currently no technique for maintaining the E and Z forms separately in a liquid sample, and therefore we cannot perform accurate absolute quantification using these standard products. This issue was addressed by converting the E form to the Z form by heat-treating the sample according to the reports by Posocco et al [25] and Marangon et al [26]. Although details of the conversion efficiency from the E to the Z form by heating have not been clarified, at least in the analysis of sunitinib N-oxide using our method, no E form of sunitinib N-oxide was detected, and no sunitinib E form was also detected when analyzed using our method, which can detect sunitinib at concentrations 20 times lower than the lower limit of detection of methods used in previous reports (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Development of a quantitative method for sunitinib N-oxide

et al. 2021

View full text Add to dashboard Cite

We developed a simple method for quantifying sunitinib N-oxide (SNO) in human serum using a supported liquid extraction (SLE) method and liquid chromatography/tandem mass spectrometry (LC-MS/MS) to assess the impact of SNO on adverse drug reactions (ADRs) caused by sunitinib. SNO was extracted using an SLE method and analyzed using an Xevo-TQ (Waters) LC-MS/MS system. SNO and voriconazole (internal standard; ISTD) were detected in ESI positive mode, with transitions at 415.4/326.3 for SNO and 350.1/281.1 for voriconazole. The retention times of SNO and voriconazole were 2.25 and 2.67 min, respectively, and good calibration curve was obtained from 0.1–5.0 ng/mL for SNO. The regression equation (weight = 1/x2) describing the calibration curve in human serum was y = 2.81 × 10-9 x2 + 0.000253 x – 0.00202 (R2 = 0.990), where y is the peak area ratio of SNO against the ISTD and x is the nominal concentration of SNO. The intra- and inter-assay accuracy varied between -2.4 and 15.6% and all data except the limit of quantification (LOQ) were within ±10%. The precision varied between 6.7–15.4% and all data except LOQ were under 15%. The mean recovery ratio of SNO was 90.3 ± 4.9%, and the mean matrix factor was 0.96 ± 0.031. This is the first report of a method to quantify SNO in blood. This method will help in elucidating the effects of SNO in humans, contribute to the elucidation of the ADRs expression factors associated with sunitinib, and aid in optimizing treatment with sunitinib.

show abstract

Section: Discussionmentioning

confidence: 99%

Development of a quantitative method for sunitinib N-oxide

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The sunitinib content in blood was determined using LC‐MS/MS. [ 50 ] 50 µL plasma was mixed with 150 µL methanol and 10 µL dasatinib in methanol (internal standard, 50 ng mL −1 ). After vertexing for 10 s, the sample was centrifuged at 13 000 rpm for 10 min at 4 °C to separate the supernatant.…”

Section: Methodsmentioning

confidence: 99%

Light‐Triggered Efficient Sequential Drug Delivery of Biomimetic Nanosystem for Multimodal Chemo‐, Antiangiogenic, and Anti‐MDSC Therapy in Melanoma

Lai

Pan

et al. 2022

Advanced Materials

View full text Add to dashboard Cite

In view of the multiple pathological hallmarks of tumors, nanosystems for the sequential delivery of various drugs whose targets are separately located inside and outside tumor cells are desired for improved cancer therapy. However, current sequential delivery is mainly achieved through enzyme‐ or acid‐dependent degradation of the nanocarrier, which would be influenced by the heterogeneous tumor microenvironment, and unloading efficiency of the drug acting on the target outside tumor cells is usually unsatisfactory. Here, a light‐triggered sequential delivery strategy based on a liposomal formulation of doxorubicin (DOX)‐loaded small‐sized polymeric nanoparticles (DOX‐NP) and free sunitinib in the aqueous cavity, is developed. The liposomal membrane is doped with photosensitizer porphyrin–phospholipid (PoP) and hybridized with red blood cell membrane to confer biomimetic features. Near‐infrared light‐induced membrane permeabilization triggers the “ultrafast” and “thorough” release of sunitinib (100% release in 5 min) for antiangiogenic therapy and also myeloid‐derived suppressor cell (MDSC) inhibition to reverse the immunosuppressive tumor environment. Subsequently, the small‐sized DOX‐NP liberated from the liposomes is more easily uptaken by tumor cells for improved immunogenic chemotherapy. RNA sequencing and immune‐related assay indicates therapeutic immune enhancement. This light‐triggered sequential delivery strategy demonstrates the potency in cancer multimodal therapy against multiple targets in different spatial positions in tumor microenvironment.

show abstract

“…The narrow therapeutic window and the positive ratio of exposure to the effectiveness of sunitinib indicates the need for its therapeutic drug monitoring. For the determination of sunitinib and its active metabolite N -desethyl sunitinib in patients’ plasma samples, the LC-MS/MS method was applied [ 40 ]. In solution, sunitinib and N -desethyl sunitinib undergo photoisomerization and procedures of samples collection and handling under strict light protection.…”

Section: Anticancer Drugsmentioning

confidence: 99%

“… MS/MS mass spectra of sunitinib (SUN) ( a ) and N -desethyl SUN ( b ) with chemical structures and identification of the main fragment ions (CE = 30 V); the 238 m/z fragment was obtained with CE = 60 V for both the analytes [ 40 ]. …”

Section: Figurementioning

confidence: 99%

Review of Chromatographic Methods Coupled with Modern Detection Techniques Applied in the Therapeutic Drugs Monitoring (TDM)

Tuzimski

Petruczynik

2020

Molecules

View full text Add to dashboard Cite

Therapeutic drug monitoring (TDM) is a tool used to integrate pharmacokinetic and pharmacodynamics knowledge to optimize and personalize various drug therapies. The optimization of drug dosing may improve treatment outcomes, reduce toxicity, and reduce the risk of developing drug resistance. To adequately implement TDM, accurate and precise analytical procedures are required. In clinical practice, blood is the most commonly used matrix for TDM; however, less invasive samples, such as dried blood spots or non-invasive saliva samples, are increasingly being used. The choice of sample preparation method, type of column packing, mobile phase composition, and detection method is important to ensure accurate drug measurement and to avoid interference from matrix effects and drug metabolites. Most of the reported procedures used liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) techniques due to its high selectivity and sensitivity. High-performance chromatography with ultraviolet detection (HPLC-UV) methods are also used when a simpler and more cost-effective methodology is desired for clinical monitoring. The application of high-performance chromatography with fluorescence detection (HPLC-FLD) with and without derivatization processes and high-performance chromatography with electrochemical detection (HPLC-ED) techniques for the analysis of various drugs in biological samples for TDM have been described less often. Before chromatographic analysis, samples were pretreated by various procedures—most often by protein precipitation, liquid–liquid extraction, and solid-phase extraction, rarely by microextraction by packed sorbent, dispersive liquid–liquid microextraction. The aim of this article is to review the recent literature (2010–2020) regarding the use of liquid chromatography with various detection techniques for TDM.

show abstract

A new high-performance liquid chromatography–tandem mass spectrometry method for the determination of sunitinib and N-desethyl sunitinib in human plasma: Light-induced isomerism overtaking towards therapeutic drug monitoring in clinical routine

Cited by 10 publications

References 27 publications

Development of a quantitative method for sunitinib N-oxide

Development of a quantitative method for sunitinib N-oxide

Light‐Triggered Efficient Sequential Drug Delivery of Biomimetic Nanosystem for Multimodal Chemo‐, Antiangiogenic, and Anti‐MDSC Therapy in Melanoma

Review of Chromatographic Methods Coupled with Modern Detection Techniques Applied in the Therapeutic Drugs Monitoring (TDM)

Contact Info

Product

Resources

About