Limits...
Quantitative and qualitative analysis of the novel antitumor 1,3,4-oxadiazole derivative (GLB) and its metabolites using HPLC-UV and UPLC-QTOF-MS.

Li P, Wang X, Li J, Meng ZY, Li SC, Li ZJ, Lu YY, Ren H, Lou YQ, Lu C, Dou GF, Zhang GL - Sci Rep (2015)

Bottom Line: Fructose-based 3-acetyl-2,3-dihydro-1,3,4-oxadiazole (GLB) is a novel antitumor agent and belongs to glycosylated spiro-heterocyclic oxadiazole scaffold derivative.The lower limit of quantification was 10 ng/mL.Our results indicated that the di-hydroxylation (M1) and hydroxylation (M2) of GLB are the major metabolites.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, PR. China.

ABSTRACT
Fructose-based 3-acetyl-2,3-dihydro-1,3,4-oxadiazole (GLB) is a novel antitumor agent and belongs to glycosylated spiro-heterocyclic oxadiazole scaffold derivative. This research first reported a simple, specific, sensitive and stable high performance liquid chromatography-ultraviolet detector (HPLC-UV) method for the quantitative determination of GLB in plasma. In this method, the chromatographic separation was achieved with a reversed phase C18 column. The calibration curve for GLB was linear at 300 nm. The lower limit of quantification was 10 ng/mL. The precision, accuracy and stability of the method were validated adequately. This method was successfully applied to the pharmacokinetic study in rats for detection of GLB after oral administration. Moreover, the structures of parent compound GLB and its two major metabolites M1 and M2 were identified in plasma using an ultra performance liquid chromatography-electrospray ionization-quadrupole-time of flight- mass spectrometry (UPLC-ESI-QTOF-MS) method. Our results indicated that the di-hydroxylation (M1) and hydroxylation (M2) of GLB are the major metabolites. In conclusion, the present study provided valuable information on an analytical method for the determination of GLB and its metabolites in rats, can be used to support further developing of this antitumor agent.

No MeSH data available.


Related in: MedlinePlus

The plasma concentration-time curves(A) and semilogdataplot (the y-coordinate was logarithmic coordinates, (B) of fructose-based 3-acetyl-2,3-dihydro-1,3,4- oxadiazole (GLB) and its two metabolites M1 and M2 after single oral administration in rat (100 mg/kg, n = 6).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4493701&req=5

f2: The plasma concentration-time curves(A) and semilogdataplot (the y-coordinate was logarithmic coordinates, (B) of fructose-based 3-acetyl-2,3-dihydro-1,3,4- oxadiazole (GLB) and its two metabolites M1 and M2 after single oral administration in rat (100 mg/kg, n = 6).

Mentions: The validated bioanalytical method was applied to the detection of GLB concentration in plasma after a single oral administration of GLB (100 mg/kg, n = 6) in rats. The mean plasma concentration–time curves of GLB, metabolites M1 and M2 are shown in Fig. 2A. At 0.5 h after oral administration, the prototype drug of GLB was detected in rat plasma. The peak concentration of GLB was at 6 h (2.78 ± 0.89 μg/mL) with quantifiable at the 36 h (0.14 ± 0.18 μg/mL). At 96 h time point, low concentration of GLB was still detectable in rat plasma (Fig. 2B). As shown in Table 3, pharmacokinetics of GLB was analyzed by non-compartmental model and the parameters were calculated as follows: Cmax was 2.78 ± 0.89 μg/mL, Tmax was 6 h. Moreover, the corresponding values for t1/2, AUC0→96 and AUC0-∞ were 9.24 ± 4.74 h, 33.30 ± 9.10 mg/L·h and 33.49 ± 9.05 mg/L·h respectively. These results suggest that the absorption and elimination of GLB might be slowly in rats and the specific reasons remained to be studied in future experiments.


Quantitative and qualitative analysis of the novel antitumor 1,3,4-oxadiazole derivative (GLB) and its metabolites using HPLC-UV and UPLC-QTOF-MS.

Li P, Wang X, Li J, Meng ZY, Li SC, Li ZJ, Lu YY, Ren H, Lou YQ, Lu C, Dou GF, Zhang GL - Sci Rep (2015)

The plasma concentration-time curves(A) and semilogdataplot (the y-coordinate was logarithmic coordinates, (B) of fructose-based 3-acetyl-2,3-dihydro-1,3,4- oxadiazole (GLB) and its two metabolites M1 and M2 after single oral administration in rat (100 mg/kg, n = 6).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493701&req=5

f2: The plasma concentration-time curves(A) and semilogdataplot (the y-coordinate was logarithmic coordinates, (B) of fructose-based 3-acetyl-2,3-dihydro-1,3,4- oxadiazole (GLB) and its two metabolites M1 and M2 after single oral administration in rat (100 mg/kg, n = 6).
Mentions: The validated bioanalytical method was applied to the detection of GLB concentration in plasma after a single oral administration of GLB (100 mg/kg, n = 6) in rats. The mean plasma concentration–time curves of GLB, metabolites M1 and M2 are shown in Fig. 2A. At 0.5 h after oral administration, the prototype drug of GLB was detected in rat plasma. The peak concentration of GLB was at 6 h (2.78 ± 0.89 μg/mL) with quantifiable at the 36 h (0.14 ± 0.18 μg/mL). At 96 h time point, low concentration of GLB was still detectable in rat plasma (Fig. 2B). As shown in Table 3, pharmacokinetics of GLB was analyzed by non-compartmental model and the parameters were calculated as follows: Cmax was 2.78 ± 0.89 μg/mL, Tmax was 6 h. Moreover, the corresponding values for t1/2, AUC0→96 and AUC0-∞ were 9.24 ± 4.74 h, 33.30 ± 9.10 mg/L·h and 33.49 ± 9.05 mg/L·h respectively. These results suggest that the absorption and elimination of GLB might be slowly in rats and the specific reasons remained to be studied in future experiments.

Bottom Line: Fructose-based 3-acetyl-2,3-dihydro-1,3,4-oxadiazole (GLB) is a novel antitumor agent and belongs to glycosylated spiro-heterocyclic oxadiazole scaffold derivative.The lower limit of quantification was 10 ng/mL.Our results indicated that the di-hydroxylation (M1) and hydroxylation (M2) of GLB are the major metabolites.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, PR. China.

ABSTRACT
Fructose-based 3-acetyl-2,3-dihydro-1,3,4-oxadiazole (GLB) is a novel antitumor agent and belongs to glycosylated spiro-heterocyclic oxadiazole scaffold derivative. This research first reported a simple, specific, sensitive and stable high performance liquid chromatography-ultraviolet detector (HPLC-UV) method for the quantitative determination of GLB in plasma. In this method, the chromatographic separation was achieved with a reversed phase C18 column. The calibration curve for GLB was linear at 300 nm. The lower limit of quantification was 10 ng/mL. The precision, accuracy and stability of the method were validated adequately. This method was successfully applied to the pharmacokinetic study in rats for detection of GLB after oral administration. Moreover, the structures of parent compound GLB and its two major metabolites M1 and M2 were identified in plasma using an ultra performance liquid chromatography-electrospray ionization-quadrupole-time of flight- mass spectrometry (UPLC-ESI-QTOF-MS) method. Our results indicated that the di-hydroxylation (M1) and hydroxylation (M2) of GLB are the major metabolites. In conclusion, the present study provided valuable information on an analytical method for the determination of GLB and its metabolites in rats, can be used to support further developing of this antitumor agent.

No MeSH data available.


Related in: MedlinePlus