کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5138033 | 1494595 | 2017 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Determination of prodrug treosulfan and its biologically active monoepoxide in rat plasma, liver, lungs, kidneys, muscle, and brain by HPLC-ESI-MS/MS method
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کلمات کلیدی
TREOLLOQESIR.T.HSCTEMATreosulfan - treosulfanRefractive index detector - آشکارساز شاخص انکساریEuropean Medicines agency - آژانس دارویی اروپاMatrix effect - اثر ماتریکس یا اثر زمینهinternal standard - استاندارد داخلیValidation - اعتبار سنجیstandard deviation - انحراف معیارDistribution - توزیعAnimals - حیواناتrid - خلاص شدن از شرRoom temperature - دمای اتاقCoefficient of Variation - ضریب تغییرPharmacokinetics - فارماکوکینتیکlower limit of quantitation - محدودیت پایین کمیتProdrug - پروتئینHematopoietic stem cell transplantation - پیوند مغز استخوانelectrospray ionization - یونیزاسیون الکترو اسپری
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Determination of prodrug treosulfan and its biologically active monoepoxide in rat plasma, liver, lungs, kidneys, muscle, and brain by HPLC-ESI-MS/MS method Determination of prodrug treosulfan and its biologically active monoepoxide in rat plasma, liver, lungs, kidneys, muscle, and brain by HPLC-ESI-MS/MS method](/preview/png/5138033.png)
چکیده انگلیسی
A prodrug treosulfan (TREO) is currently investigated in clinical trials for conditioning prior to hematopoietic stem cell transplantation. Bioanalysis of TREO and its active derivatives, monoepoxide (S,S-EBDM) and diepoxide, in plasma and urine underlay the pharmacokinetic studies of these compounds but cannot explain an organ pharmacological action or toxicity. Recently, distribution of TREO and S,S-EBDM into brain, cerebrospinal fluid, and aqueous humor of the eye has been investigated in animal models and the obtained results presented clinical relevance. In this paper, a selective and rapid HPLC-ESI-MS/MS method was elaborated and validated for the studies of disposition of TREO and S,S-EBDM in rat plasma, liver, lungs, kidneys, muscle, and brain. The two analytes and codeine, internal standard (IS), were isolated from 50 μL of plasma and 100 μL of supernatants of the tissues homogenates using ultrafiltration Amicon vials. Chromatographic resolution was accomplished on C18 column with isocratic elution. The limits of quantitation of TREO and S,S-EBDM in the studied matrices ranged from 0.11 to 0.93 μM. The HPLC-MS/MS method was adequately precise and accurate within and between runs. The IS-normalized matrix effect differed among the tissues and was the most pronounced in a liver homogenate supernatant (approximately 0.55 for TREO and 0.35 for S,S-EBDM). Stability of the analytes in experimental samples was also established. The validated method for the first time enabled determination of TREO and S,S-EBDM in the six life-important tissues in rats following administration of the prodrug.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical and Biomedical Analysis - Volume 140, 5 June 2017, Pages 122-129
Journal: Journal of Pharmaceutical and Biomedical Analysis - Volume 140, 5 June 2017, Pages 122-129
نویسندگان
MichaÅ RomaÅski, Anna Kasprzyk, Artur Teżyk, Agnieszka Widerowska, CzesÅaw Å»aba, Franciszek GÅówka,