A validated LC–MS/MS method for the simultaneous determination of thalidomide and its two metabolites in human plasma: Application to a pharmacokinetic assay

Xiang, Peng; Cai, Dake; Wen, Dingsheng; Liu, Yao; Mao, Zhi; Chen, Jiangying; Hu, Pinjin; Wang, Xueding; Gao, Yujie; Huang, Min; Gao, Xiang; Zhong, Guoping

doi:10.1002/bmc.4240

Cited by 4 publications

(2 citation statements)

References 16 publications

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“…Knowing there are several modified physiological parameters in the GI tract of CD patients, the number of cases that passed the rigor of the inclusion criteria was not sufficiently high to indicate a consistent trend. For instance, the exposure of CYP3A substrates did not show the same magnitude of change [ 39 , 42 , 43 , 50 – 56 ] in the same phase of the disease (active/inactive). Also, when S - and R -verapamil [ 50 ] and midazolam and budesonide [ 39 ] were given to the same CD patients, the exposure behaviour was not similar.…”

Section: Resultsmentioning

confidence: 99%

Altered Bioavailability and Pharmacokinetics in Crohn’s Disease: Capturing Systems Parameters for PBPK to Assist with Predicting the Fate of Orally Administered Drugs

Alrubia

Mao²,

Chen³

et al. 2022

Clin Pharmacokinet

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Backgrond and Objective Crohn’s disease (CD) is a chronic inflammatory bowel disease that affects a wide age range. Hence, CD patients receive a variety of drugs over their life beyond those used for CD itself. The changes to the integrity of the intestine and its drug metabolising enzymes and transporters (DMETs) can alter the oral bioavailability of drugs. However, there are other changes in systems parameters determining the fate of drugs in CD, and understanding these is essential for dose adjustment in patients with CD. Methods The current analysis gathered all the available clinical data on the kinetics of drugs in CD (by March 2021), focusing on orally administered small molecule drugs. A meta-analysis of the systems parameters affecting oral drug pharmacokinetics was conducted. The systems information gathered on intestine, liver and blood proteins and other physiological parameters was incorporated into a physiologically based pharmacokinetic (PBPK) platform to create a virtual population of CD patients, with a view for guiding dose adjustment in the absence of clinical data in CD. Results There were no uniform trends in the reported changes in reported oral bioavailability. The nature of the drug as well as the formulation affected the direction and magnitude of variation in kinetics in CD patients relative to healthy volunteers. Even for the same drug, the reported changes in exposure varied, possibly due to a lack of distinction between the activity states of CD. The highest alteration was seen with S -verapamil and midazolam, 8.7- and 5.3-fold greater exposure, respectively, in active CD patients relative to healthy volunteers. Only one report was available on liver DMETs in CD, and indicated reduced CYP3A4 activity. In a number of reports, mRNA expression of DMETs in the ileum and colon of CD patients was measured, focussing on P-glycoprotein (p-gp) transporter and CYP3A4 enzyme, and showed contradictory results. No data were available on protein expression in duodenum and jejunum despite their dominant role in oral drug absorption. Conclusion There are currently inadequate dedicated clinical or quantitative proteomic studies in CD to enable predictive PBPK models with high confidence and adequate verification. The PBPK models for CD with the available systems parameters were able to capture the major physiological influencers and the gaps to be filled by future research. Quantification of DMETs in the intestine and the liver in CD is warranted, alongside well-defined clinical drug disposition studies with a number of index drugs as biomarkers of changes in DMETs in these patients, to avoid large-scale dedicated studies for every drug to determine the effects of disease on the drug’s metabolism and disposition and the consequential safety and therapeutic concerns. Supplementary Information The online version contains supplementary material av...

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Section: Resultsmentioning

confidence: 99%

Altered Bioavailability and Pharmacokinetics in Crohn’s Disease: Capturing Systems Parameters for PBPK to Assist with Predicting the Fate of Orally Administered Drugs

Alrubia

Mao²,

Chen³

et al. 2022

Clin Pharmacokinet

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“…Thalidomide is 2-[(3R)-2,6-dioxopiperidin-3-yl]-2,3-dihydro-1 H -isoindole-1,3-dione ( Figure 1 ) [ 5 ]. Thalidomide was determined by different chromatographic methods [ 10 , 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Selective Sensing of Darolutamide and Thalidomide in Pharmaceutical Preparations and in Spiked Biofluids

2022

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Selective spectrofluorometric sensing is introduced for the analysis of non-steroidal anti-androgens, darolutamide, and thalidomide in pharmaceutical preparations and biofluids. An organic fluorophore, 2,4,8,10-tetramethylpyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine 2 was synthesized in our laboratories by new simple methods to act as a fluorescent reagent for the analysis of the studied drugs. Elemental and spectral analyses were performed to approve the fluorophore structure. The fluorophore possesses a fluorescence at λem 422 nm when excited at 328 nm. The interaction between the studied drugs and the fluorophore was found to be quenching. The quenching mechanisms were studied and interpreted through the Stern–Volmer relationship. Moreover, the Stern–Volmer constants were calculated for the quenching interactions of both drugs. The introduced method was validated for the estimation of darolutamide and thalidomide in dosage forms, plasma, and urine, offering good percentage recoveries.

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Simultaneous quantification of thalidomide, lenalidomide and pomadomide in plasma by LC-MS/MS

Wang

Qiang²,

Jia

et al. 2023

Journal of Pharmacological and Toxicological Methods

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A validated LC–MS/MS method for the simultaneous determination of thalidomide and its two metabolites in human plasma: Application to a pharmacokinetic assay

Cited by 4 publications

References 16 publications

Altered Bioavailability and Pharmacokinetics in Crohn’s Disease: Capturing Systems Parameters for PBPK to Assist with Predicting the Fate of Orally Administered Drugs

Altered Bioavailability and Pharmacokinetics in Crohn’s Disease: Capturing Systems Parameters for PBPK to Assist with Predicting the Fate of Orally Administered Drugs

Selective Sensing of Darolutamide and Thalidomide in Pharmaceutical Preparations and in Spiked Biofluids

Simultaneous quantification of thalidomide, lenalidomide and pomadomide in plasma by LC-MS/MS

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