Normal phase and reverse phase HPLC-UV-MS analysis of process impurities for rapamycin analog ABT-578: Application to active pharmaceutical ingredient process development

Chen, Yong; Brill, G.; Benz, Nancy J.; Leanna, M. Robert; Dhaon, Madhup K.; Rasmussen, Michael; Zhou, Casey Chun; Bruzek, James A.; Bellettini, John R.

doi:10.1016/j.jchromb.2007.08.012

Cited by 11 publications

(4 citation statements)

References 26 publications

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“…Analysis was carried out for RPM by reverse phase HPLC (RP-HPLC) (Shimadzu UFLC model) on C-18 column Inertsil Õ (Octadecylsilane[ODS]-3 V, dimension 4.6 Â 250 mm) with a mobile phase of methanol-water (90:10 v/v) in isocratic mode at a flow rate of 1 ml/min with 278 nm as the analytical wavelength and 20 ml injection volume Khan et al, 2013). Similarly for PIP, analysis was carried out by RP-HPLC (Shimadzu UFLC model) on C-18 column Inertsil Õ (ODS-3 V, dimension 4.6 Â 250 mm) with a mobile phase of acetonitrile-water (60:40 v/v) in isocratic mode at a flow rate of 1.5 ml/min with 343 nm as analytical wavelength and 20 ml injection volume (Chen et al, 2007). Calibration curves were prepared in the concentration range of 0.1-50 and 0.25-50 mg/ml for RPM and PIP, respectively.…”

Section: Entrapment Efficiency Of Nanoparticlesmentioning

confidence: 99%

Co-delivery of rapamycin- and piperine-loaded polymeric nanoparticles for breast cancer treatment

et al. 2015

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P-glycoprotein (P-gp) efflux is the major cause of multidrug resistance (MDR) in tumors when using anticancer drugs, moreover, poor bioavailability of few drugs is also due to P-gp efflux in the gut. Rapamycin (RPM) is in the clinical trials for breast cancer treatment, but its P-gp substrate property leads to poor oral bioavailability and efficacy. The objective of this study is to formulate and evaluate nanoparticles of RPM, along with a chemosensitizer (piperine, PIP) for improved oral bioavailability and efficacy. Poly(d,l-lactide-co-glycolide) (PLGA) was selected as polymer as it has moderate MDR reversal activity, which may provide additional benefits. The nanoprecipitation method was used to prepare PLGA nanoparticles with particle size below 150 nm, loaded with both drugs (RPM and PIP). Prepared nanoparticles showed sustained in vitro drug release for weeks, with initial release kinetics of zero order with non-Fickian transport, subsequently followed by Higuchi kinetics with Fickian diffusion. An everted gut sac method was used to study the effect of P-gp efflux on drug transport. This reveals that the uptake of the RPM (P-gp substrate) has been increased in the presence of chemosensitizer. Pharmacokinetic studies showed better absorption profile of RPM from polymeric nanoparticles compared to its suspension counterpart and improved bioavailability of 4.8-folds in combination with a chemosensitizer. An in vitro cell line study indicates higher efficacy of nanoparticles compared to free drug solution. Results suggest that the use of a combination of PIP with RPM nanoparticles would be a promising approach in the treatment of breast cancer.

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Section: Entrapment Efficiency Of Nanoparticlesmentioning

confidence: 99%

Co-delivery of rapamycin- and piperine-loaded polymeric nanoparticles for breast cancer treatment

et al. 2015

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“…Other LC modes, such as normal phase [33,34], ion exchange [35], ion-pairing [36,37] and hydrophilic interaction chromatography (HILIC) [38,39], in addition to alternative separation methodologies, such capillary electrophoresis (CE) [40,41], have also been used, although to a lesser extent. CE stands out for its advantageous sensitivity, eco-friendliness, resolution and high efficiency; but it is not as precise as HPLC.…”

Section: General Questionsmentioning

confidence: 99%

Practical and regulatory considerations for stability-indicating methods for the assay of bulk drugs and drug formulations

Maggio

Vignaduzzo

Kaufman

2013

TrAC Trends in Analytical Chemistry

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“…Sirolimus (34; Rapamune, Wyeth) was originally discovered from bacterium Steptomyces hygroscopicus with promising antifungal activity 467,468 and is being used along with other coronary stents against restenosis of coronary arteries due to balloon angioplastyis. Zotarolimus (53) is an active principle of Endeavor™ (tradename) stent that inhibits cell proliferation, preventing scar tissue formation and minimizes restenosis in angioplasty patients [469]. In July 2005, Medtronic received European approval for the sale of the Endeavor drug-eluting coronary stent that consists of a cobalt-based alloy integrated with a biomimetic phosphorylcholine polymer.…”

Section: Dronabinol and Cannabidolmentioning

confidence: 99%

Natural Products in Drug Discovery: Impacts and Opportunities — An Assessment

Brahmachari

2011

Bioactive Natural Products

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Nature stands as an inexhaustible source of novel chemotypes and pharmacophores, and has been a source of medicinal agents for thousands of years, and an impressive number of modern drugs find their origin in natural products. Natural product chemistry has experienced explosive and diversified growth, making natural products the subject of much interest and promise in the present day research directed towards drug design and discovery. It is noteworthy that natural products are a source of new compounds with diversified structural arrangements possessing interesting biological activities. Natural products, thus, have played and continue to play an invaluable role in the drug discovery process. Recently, there has been a renewed interest in natural products research due to the failure of alternative drug discovery methods to deliver many lead compounds in key therapeutic areas such as immunosuppression, anti-infective, and metabolic diseases. However, continuing improvements in natural products research are needed to continue to be competitive with other drug discovery methods, and also to keep pace with the ongoing changes in the drug discovery process. Faithful drives are needed in a more intensified fashion to explore "Nature" as a source of novel and active agents that may serve as the leads and scaffolds for elaboration into urgently needed efficacious drugs for a multitude of disease indications. Natural products have provided considerable value to the pharmaceutical industry over the past half century. In particular, the therapeutic

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Normal phase and reverse phase HPLC-UV-MS analysis of process impurities for rapamycin analog ABT-578: Application to active pharmaceutical ingredient process development

Cited by 11 publications

References 26 publications

Co-delivery of rapamycin- and piperine-loaded polymeric nanoparticles for breast cancer treatment

Co-delivery of rapamycin- and piperine-loaded polymeric nanoparticles for breast cancer treatment

Practical and regulatory considerations for stability-indicating methods for the assay of bulk drugs and drug formulations

Natural Products in Drug Discovery: Impacts and Opportunities — An Assessment

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