Development and validation of a liquid chromatography/tandem mass spectrometry procedure for the quantification of sunitinib (SU11248) and its active metabolite, N-desethyl sunitinib (SU12662), in human plasma: Application to an explorative study

Rodamer, Michael; Elsinghorst, Paul W.; Kinzig, Martina; Gütschow, Michael; Sörgel, Fritz

doi:10.1016/j.jchromb.2011.02.006

Cited by 33 publications

(32 citation statements)

References 25 publications

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“…A possible concern in plasma analysis of TKIs is hemolysis. Several articles investigated the interference of hemolysis on matrix effect (ceritinib [22], dasatinib, sunitinib, imatinib, nilotinib, erlotinib, lapatinib, sorafenib, vandetanib [23]), precision and accuracy (sunitinib/N-desmethyl-sunitinib [24], lapatinib [25]), cross-talk, carry-over, and interference (imatinib [26,27]). They only tested spiking of either drug to hemolyzed plasma, hemolyzed blood to drug-containing plasma, or hemolytic blanks.…”

Section: Plasma and Serummentioning

confidence: 99%

“…Potentially, TKIs bound to erythrocytes could be freed during hemolysis [22][23][24][25][26][27]. This is discussed in the next section.…”

Section: Plasma and Serummentioning

confidence: 99%

“…Although HILIC is not equipped routinely in the recent years for TKIs, a method from 2009 employed the technique successfully with 1.0 minute run-times for dasatinib, nilotinib and imatinib [109]. Uses of other column-chemistries, such as phenyl-columns [52,95,100], strong cation exchange [7], or PLRP macroporous spherical polystyrene/divinylbenzene particles [24] have been employed in TKI bioanalysis, although these reports do not state any justification for their choice.…”

Section: Separation Principlesmentioning

confidence: 99%

“…Whilst concomitant administration of an CYP3A4 inhibitor would put patients at a higher risk of development of these toxicities, the use of an inducer might lower sunitinib toxicity without diminishing potency [9]. For sunitinib, multiple assays that focus on the active metabolite as well as the parent compound have been published [24,57,65,104,114,130,134]. The active O-desmethyl-metabolite of erlotinib, OSI420, is in most literature noted as the most abundant metabolite, while in fact the peak described as OSI420…”

Section: Metabolite Analysismentioning

confidence: 99%

“…52 axitinib -sulfoxide* [191] bosutinib oxydechloro-*, N-desmethyl-*, -N-oxide* [192] cabozantinib -N-oxide* [193] Decyclopropyl-, Dimethyl-, -N-oxide O-dearyl- [138] nilotinib -N-Oxide*, Hydroxy-* [195,196] nindetanib O-demethyl- [159] osimertinib N-desmethyl-* [197] pazopanib Hydroxy-*, N-demethyl-* [198] ponatinib N-desmethyl-* [199] regorafenib N-oxide-(BAY757495), N-oxide-O-desmethyl-(BAY818752) [163] ruxolitinib Hydroxy-* [200] sorafenib -N-oxide [2,114] sunitinib N-desethyl-N,N-didesethyl- [24,57,65,104,114,130,134] trametinib N-deacetyl-(M5)* [201] …”

mentioning

confidence: 99%

See 4 more Smart Citations

Recent developments in the chromatographic bioanalysis of approved kinase inhibitor drugs in oncology

Rood

Schellens

Beijnen

et al. 2016

Journal of Pharmaceutical and Biomedical Analysis

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Section: Plasma and Serummentioning

confidence: 99%

“…Potentially, TKIs bound to erythrocytes could be freed during hemolysis [22][23][24][25][26][27]. This is discussed in the next section.…”

Section: Plasma and Serummentioning

confidence: 99%

Section: Separation Principlesmentioning

confidence: 99%

Section: Metabolite Analysismentioning

confidence: 99%

mentioning

confidence: 99%

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Recent developments in the chromatographic bioanalysis of approved kinase inhibitor drugs in oncology

Rood

Schellens

Beijnen

et al. 2016

Journal of Pharmaceutical and Biomedical Analysis

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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

Rais

Zhao

et al. 2012

Biomedical Chromatography

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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 range of 0.1–100 ng/mL and 0.02–5 ng/mL for sunitinib and 0.2–200 ng/mL 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.

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Simultaneous determination of sunitinib and its two metabolites in plasma of Chinese patients with metastatic renal cell carcinoma by liquid chromatography–tandem mass spectrometry

Qiu

Bian

et al. 2012

Biomedical Chromatography

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A simple and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of sunitinib and its two metabolites in plasma of Chinese patients with metastatic renal cell carcinoma (mRCC). After simple one-step protein precipitation with methanol-acetonitrile (1:1, v/v), all three analytes were separated on an Agilent Zorbax SB-C(18) column using a gradient mobile phase consisting of water (0.1% formic acid)-acetonitrile (0.1% formic acid) at a flow rate of 0.50 mL/min. The detection was performed in multiple reaction monitoring mode, using the transitions of m/z 399.0 → 326.2, m/z 371.0 → 283.1, m/z 343.0 → 283.1 and m/z 386.3 → 122.2 for sunitinib, M1, M2 and buspirone, respectively. The method was linear over the range of 0.10-100 ng/mL for all three analytes using only 50 μL of plasma and the lower limit of quantifications for the three analytes were all 0.10 ng/mL. The intra-day and inter-day precisions were all less than 15% and the accuracies were within the range of ±15%; recoveries were between 85.0 and 115%. The validated method was successfully applied to an explorative pharmacokinetic study of sunitinib in Chinese patients with mRCC following multi-dose oral administration.

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Development and validation of a liquid chromatography/tandem mass spectrometry procedure for the quantification of sunitinib (SU11248) and its active metabolite, N-desethyl sunitinib (SU12662), in human plasma: Application to an explorative study

Cited by 33 publications

References 25 publications

Recent developments in the chromatographic bioanalysis of approved kinase inhibitor drugs in oncology

Recent developments in the chromatographic bioanalysis of approved kinase inhibitor drugs in oncology

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

Simultaneous determination of sunitinib and its two metabolites in plasma of Chinese patients with metastatic renal cell carcinoma by liquid chromatography–tandem mass spectrometry

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