High-throughput quantification of the anti-leukemia drug STI571 (Gleevec™) and its main metabolite (CGP 74588) in human plasma using liquid chromatography–tandem mass spectrometry

Bakhtiar, Ray; Lohne, Jack J.; Ramos, Luis; Khemani, L.; Hayes, M.; Tse, Francis L. S.

doi:10.1016/s1570-0232(01)00611-0

Cited by 136 publications

(98 citation statements)

References 38 publications

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“…Plasma was then isolated by centrifugation at 1900Âg for 15 min and stored at À40 1C until further analysis. IM trough concentration was determined by high-performance liquid chromatography equipped with a mass spectrometric detector from Toray Research Center, Inc. (Nihonbashi, Tokyo, Japan), 32,33 which is the only Novartis Global authorized platform in Japan.…”

Section: Measurement Of Plasma Im Concentrationmentioning

confidence: 99%

Influence of CYP3A5 and drug transporter polymorphisms on imatinib trough concentration and clinical response among patients with chronic phase chronic myeloid leukemia

et al. 2010

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Imatinib mesylate (IM) trough concentration varies among IM-treated chronic myeloid leukemia (CML) patients. Although IM pharmacokinetics is influenced by several enzymes and transporters, little is known about the role of pharmacogenetic variation in IM metabolism. In this study, associations between IM trough concentration, clinical response and 11 single-nucleotide polymorphisms in genes involved in IM pharmacokinetics (ABCB1, ABCC2, ABCG2 CYP3A5, SLC22A1 and SLCO1B3) were investigated among 67 Japanese chronic phase CML patients. IM trough concentration was significantly higher in patients with a major molecular response than in those without one (P¼0.010). No significant correlations between IM trough concentration and age, weight, body mass index or biochemical data were observed. However, the dose-adjusted IM trough concentration was significantly higher in patients with ABCG2 421A than in those with 421C/C (P=0.015). By multivariate regression analysis, only ABCG2 421A was independently predictive of a higher dose-adjusted IM trough concentration (P¼0.015). Moreover, previous studies have shown that the ABCG2 421C4A (p.Q141K) variant is prevalent among Japanese and Han Chinese individuals and less common among Africans and Caucasians. Together, these data indicate that plasma IM concentration monitoring and prospective ABCG2 421C4A genotyping may improve the efficacy of IM therapy, particularly among Asian CML patients.

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Section: Measurement Of Plasma Im Concentrationmentioning

confidence: 99%

Influence of CYP3A5 and drug transporter polymorphisms on imatinib trough concentration and clinical response among patients with chronic phase chronic myeloid leukemia

et al. 2010

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“…The assays were based on rapid, simple and sensitive protocols that had been validated earlier. 35,36 There are other methods, such as HPLC coupled with UVdiode array detection, which can be used to quantify imatinib. However, these alternative assays must be validated to current guidelines stipulated by the FDA or another regulatory body, and ideally also cross validated against the already validated LC-MS/MS reference method.…”

Section: Trough Plasma Concentrationsmentioning

confidence: 99%

Pharmacokinetic/pharmacodynamic correlation and blood-level testing in imatinib therapy for chronic myeloid leukemia

et al. 2009

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“…16 Imatinib therapy in CML requires chronic drug intake. A patient receives their daily dosage regimen every 12 or 24 hours depending on the limitation of the daily dose they are clinically assigned to.…”

Section: Discussionmentioning

confidence: 99%

Imatinib and Norimatinib Plasma Levels Analyses of Chronic Myeloid Leukemia Patients

Kilic¹,

Kayaaltı²,

Gündüz³

et al. 2016

Turkiye Klinikleri J Pharm Sci

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A AB BS S T TR RA AC CT T O Ob bj je ec ct ti iv ve e: : Imatinib is the first line treatment in chronic myeloid leukemia (CML). Imatinib metabolism depends primarily on the presence of cytochrome P450 enzymes, its active metabolite being norimatinib (N-desmethyl imatinib). Norimatinib accumulates in plasma 10-30%. The aim of this study was to analyze certain parameters which maintain the importance in clarifying the pharmacologic effects of imatinib. M Ma at te er ri ia al l a an nd d M Me et th ho od ds s: : To investigate plasma concentrations, 41 CML patients on minimum 400 mg imatinib daily were included to the study. Pharmacokinetic analysis was performed by tandem mass spectrometry (LC-MS/MS). Mean plasma imatinib and norimatinib levels were statistically calculated as 4.038±1.290 ppm (min. 0.576 ppm, max. 6.795 ppm) and 1.150±0.733 ppm (min. 0.08 ppm, max. 3.835 ppm), respectively. R Re es su ul lt ts s: : Limit of detection (LOD) values for imatinib and norimatinib were 30 ppb and 25 ppb, whereas limit of quantification (LOQ) values were 99 ppb and 82.5 ppb, and recovery of imatinib and norimatinib were 98.45% and 92.47%, respectively. Average percentage of imatinib transformation to norimatinib was 22.16%. Variation of this percentage from one patient to another suggested the possibility of interindividual differences in drug response. C Co on nc cl lu us si io on n: : Individual results have shown that pharmacologic effects of imatinib may differentiate among patients. In this study, we standardized and justified the applicability of our analysis method. Patients' plasma drug levels can be measured using this method. Thus optimal treatment efficacy can be ensured.K Ke ey y W Wo or rd ds s: : İmatinib; pharmacokinetics; drug monitoring; leukemia, myeloid, chronic-phase; tandem mass spectrometry Ö ÖZ ZE ET T A Am ma aç ç: : İmatinib, kronik miyeloid lösemi tedavisinde ilk tercih edilen tedavi yöntemidir. İma-tinib metabolizması temelde sitokrom P450 enzimleri üzerinden, aktif metaboliti norimatinibe (Ndesmetil imatinibe) dönüşme şeklinde yürür. Norimatinib plazmada %10-30 aralığında birikme gösterir. Bu çalışmanın amacı, imatinibin farmakolojik etkilerini aydınlatmaya yardımcı olan parametrelerin analiz edilmesidir. G Ge er re eç ç v ve e Y Yö ön nt te em ml le er r: : Plazma konsantrasyonlarının araştırılmasında, çalışmaya, günde en az 400 mg imatinib tedavisi gören 41 KML hastası dahil edildi. Plazma analizleri, tekrarlayan kütle spektrometrisi (LC-MS/MS) ile gerçekleştirildi. Ortalama plazma imatinib ve norimatinib düzeyleri istatistiksel yöntemlerle sırasıyla 4,038±1,290 ppm (min. 0,576 ppm, maks. 6,795 ppm) ve 1,150±0,733 ppm (min. 0,08 ppm, maks. 3,835 ppm) olarak hesaplandı. B Bu ul lg gu ul la ar r: : İmatinib ve norimatinib için saptama sınırı (LOD) değerleri sırasıyla 30 ppb ve 25 ppb, miktar tayini (LOQ) değerleri ise sırasıyla 99 ppb ve 82,5 ppb ve imatinib ile norimatinib için yüzde kazanım sırasıyla %98,45 ve %92,47 bulundu. İmatinibin norimatinibe ortalama dönüşüm yüzdesi %22,16 olarak he...

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High-throughput quantification of the anti-leukemia drug STI571 (Gleevec™) and its main metabolite (CGP 74588) in human plasma using liquid chromatography–tandem mass spectrometry

Cited by 136 publications

References 38 publications

Influence of CYP3A5 and drug transporter polymorphisms on imatinib trough concentration and clinical response among patients with chronic phase chronic myeloid leukemia

Influence of CYP3A5 and drug transporter polymorphisms on imatinib trough concentration and clinical response among patients with chronic phase chronic myeloid leukemia

Pharmacokinetic/pharmacodynamic correlation and blood-level testing in imatinib therapy for chronic myeloid leukemia

Imatinib and Norimatinib Plasma Levels Analyses of Chronic Myeloid Leukemia Patients

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