Development and validation of a UPLC–MS/MS method for quantification of SKLB010, an investigational anti-inflammatory compound, and its application to pharmacokinetic studies in beagle dogs

Xia, Ye; Tang, Minghai; Liu, Juan; Li, Linyu; Ma, Liang; Zheng, Hao; Hu, Jia; Chen, Xiang; Duan, Xingmei; Chen, Lijuan

doi:10.1016/j.jpba.2011.05.031

Cited by 5 publications

(2 citation statements)

References 19 publications

(22 reference statements)

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“…Total lipids were extracted using Folch’s method 54 and analysed by LC-MS as previously described 55 . Briefly, freshly harvested cells were homogenized by chloroform/methanol (2:1, v-v).…”

Section: Methodsmentioning

confidence: 99%

Deletions linked to TP53 loss drive cancer through p53-independent mechanisms

Liu

Chen

et al. 2016

Nature

228

202

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Mutations disabling the TP53 tumour suppressor gene represent the most frequent events in human cancer and typically occur through a two-hit mechanism involving a missense mutation in one allele and a ‘loss of heterozygosity’ deletion encompassing the other. While TP53 missense mutations can also contribute gain-of-function activities that impact tumour progression, it remains unclear whether the deletion event, which frequently includes many genes, impacts tumorigenesis beyond TP53 loss alone. Here we show that somatic heterozygous deletion of mouse chromosome 11B3, a 4-megabase region syntenic to human 17p13.1, produces a greater effect on lymphoma and leukaemia development than Trp53 deletion. Mechanistically, the effect of 11B3 loss on tumorigenesis involves co-deleted genes such as Eif5a and Alox15b (also known as Alox8), the suppression of which cooperates with Trp53 loss to produce more aggressive disease. Our results imply that the selective advantage produced by human chromosome 17p deletion reflects the combined impact of TP53 loss and the reduced dosage of linked tumour suppressor genes.

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Section: Methodsmentioning

confidence: 99%

Deletions linked to TP53 loss drive cancer through p53-independent mechanisms

Liu

Chen

et al. 2016

Nature

228

202

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“…The use of beagle dogs to study the pharmacokinetics of drugs was reported by several researchers [25][26][27] . Beagle dogs represent a standard non-rodent species used in preclinical pharmacokinetics and tissue distribution studies.…”

Section: Pharmacokinetics and Oral Bioavailability Studymentioning

confidence: 99%

Powdered self-emulsified lipid formulations of meloxicam as solid dosage forms for oral administration

Agarwal¹,

Alayoubi²,

Siddiqui³

et al. 2012

Drug Development and Industrial Pharmacy

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The objectives of this study were to prepare a powdered self-emulsified (SEDDS) formulation of meloxicam and to compare its oral bioavailability against commercial Mobic tablets. The SEDDS formulation was prepared by in situ salt formation of meloxicam in a blend of lipid excipients and aqueous tris (hydroxymethyl) aminomethane solution. The liquid SEDDS was subsequently adsorbed on silica powder and was tested for size, flow, and crystal growth. The flowability index of the powdered SEDDS was borderline acceptable. Absence of crystal growth with storage was confirmed by DSC and PXRD studies. Dissolution of meloxicam from the powdered SEDDS was >90% vs. <12% for powdered meloxicam and <80% for the commercial tablets. Stability of the powdered formulations after storage in gelatin and HPMC capsules was also evaluated to study the effect of water migration from the fill into capsule shells. Capsules softened to a different extent as a function of fill material with HPMC capsules showing greater resistance to water migration. Finally, oral bioavailability of the formulations was evaluated in beagle dogs. Powdered meloxicam SEDDS formulation showed a 1.3-fold increase in AUC vs. commercial Mobic® tablets. Overall, this study described a novel SEDDS formulation of meloxicam and outlined a systematic approach to adsorbing and testing the flow and stability behavior of powdered SEDDS formulations.

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Ultra‐high‐performance liquid chromatography tandem mass spectrometry method for the determination of gambogenic acid in dog plasma and its application to a pharmacokinetic study

Chen

Wang

et al. 2014

Biomedical Chromatography

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A highly sensitive and rapid ultra-high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of gambogenic acid in dog plasma. Gambogic acid was used as an internal standard (IS). After a simple liquid-liquid extraction by ethyl acetate, the analyte and internal standard were separated on an Acquity BEH C18 (100 × 2.1 mm, 1.7 µm; Waters ) column at a flow rate of 0.2 mL/min, using 0.1% formic acid-methanol (10:90, v/v) as mobile phase. Electrospray ionization source was applied and operated in the positive ion mode. Multiple reaction monitoring mode with the transitions m/z 631.3 → 507.3 and m/z 629.1 → 573.2 was used to quantify gambogenic acid and the internal standard, respectively. The calibration curves were linear in the range of 5-1000 ng/mL, with a coefficient of determination (r) of 0.999 and good calculated accuracy and precision. The low limit of quantification was 5 ng/mL. The intra-and inter-day precisions (relative standard deviations) were <15%. The methodology recoveries were more than 66.63%. This validated method was successfully applied to a pharmacokinetic study after intravenous injection administration of gambogenic acid in dogs at a dose of 1 mg/kg.

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Development and validation of a UPLC–MS/MS method for quantification of SKLB010, an investigational anti-inflammatory compound, and its application to pharmacokinetic studies in beagle dogs

Cited by 5 publications

References 19 publications

Deletions linked to TP53 loss drive cancer through p53-independent mechanisms

Deletions linked to TP53 loss drive cancer through p53-independent mechanisms

Powdered self-emulsified lipid formulations of meloxicam as solid dosage forms for oral administration

Ultra‐high‐performance liquid chromatography tandem mass spectrometry method for the determination of gambogenic acid in dog plasma and its application to a pharmacokinetic study

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