Background: Curcumin has several pharmacological effects including anti-inflammatory, antioxidant, antiviral, antifungal, antibacterial, immunomodulatory, hepatoprotector, inhibiting tumor growth, angiogenesis and inducing apoptosis by inhibiting the PI3K/Akt signal pathway in ovarian cancer cells. Curcumin can reduce kidney damage through suppression of mTOR effector pathways, NF-κB inhibition, TNF-α and IL-6. However the use of curcumin in vivo is limited because curcumin is hydrophobic, has low bioavailability and low capacity to reach target organs. This limitation is overcome by increasing the solubility of curcumin and making it in the form of nanoparticles. We have already develop new formulation of nanocurcumin consist of chitosan and NaTPP as a polymer.

Aim: Validating the determination of curcumin levels on tissue homogenates, measuring the  curcumin level on liver, kidney and ovarian homogenates in healthy rat groups and rat ovarian cancer models that given two form of curcumin, i.e conventional curcumin and nanocurcumin.

Method: Measurement of curcumin levels in homogenate using UPLC-MS/MS. Separation of analyte in the sample using liquid chromatography system with Acquity UPLC® BEH C18 column and mobile phase gradient using 0.1% formic acid and acetonitrile with a ratio of 72:28. Validation method to determining curcumin levels on organ homogenates, including parameters of accuracy and precision (half validation). Determination of curcumin level in the organ healthy rats was carried out in 2 treatment groups. Group that received curcumin and group that received nanocurcumin orally with a single dose of 100 mg/kgBB. At 180 minutes, rats were decapitated for liver, kidney and ovaries. The other group of rat that develop ovarian cancer  were also divided into 2 groups and given curcumin and nanocurcumin with repeated doses of 100 mg/kgBW for 30 days.

Results: In organ homogenates, the mean concentration and coefficient of variation of within run accuracy and precision were 96.33%–107.58% and 3.34%–6,89%, respectively. In the group that received curcumin, curcumin was not detect in the liver, kidney and ovaries (0.00 ± 0.00 ng/mL), whereas in the group that received nanocurcumin, the levels of curcumin are 1.866,6 ± 22.60 ng/g were obtained in liver, 114,873 ± 13,36 ng/g in kidney and 136,864 ± 11,15 ng/g in ovarian. In ovarian cancer rats, the group receiving curcumin obtained levels of curcumin is 2.288 ± 1.15 ng/g and 17.76 ± 4.85 ng/g in the group receiving nanocurcumin.

Conclusion: UPLC MS/MS can detect minimal amounts of curcumin in rat organ and curcumin nanoparticles can increase the distribution of curcumin in liver, kidney, ovaries tissue and as well as in the ovaries cancer model rats

Keyword: curcumin, UPLC MS/MS, rat organ, ovarian cancer rats

Author

Ni Made Dwi Sandhiutami1,2, Wawaimuli Arozal3*, Melva Louisa3, Deni Rahmat2

1Doctoral Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, INDONESIA.
2Faculty of Pharmacy, University of Pancasila, Jakarta, INDONESIA.
3Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta, INDONESIA.