Comparative research on stability of baicalin and baicalein administrated in monomer and total flavonoid fraction form of Radix scutellariae in biological fluids in vitro

Abstract

Context: Baicalin (BL) and baicalein (B) as the major flavonoids of Scutellaria baicalensis Georgi (Lamiaceae) have been investigated intensively, and shown to possess a multitude of pharmacological activities.

Objective: This study systematically evaluates the stability of BL and B in monomer and total flavonoid fraction (FSR) form in vitro, and further studies whether the protective measures are effective to make B and BL stable enough to meet the requirement of quantitative analysis in various biological samples.

Materials and methods: The stability of BL and B was evaluated by investigating the influence factors such as pH (2.0, 3.0, 4.5, 6.8, 7.4 and 9.0), temperature (4, 25 and 40 °C), antioxidant (vitamin C and Na₂SO₃) and sunlight. After the protective measures were taken, stability of BL and B in plasma, urine and tissue homogenates was evaluated through post-preparative stability (stored at 4 °C for 24 h), three freeze–thaw cycles stability and long-term stability test (stored in refrigerator at −20 °C for 15 days). In addition, by comparing the degradation parameters of BL and B obtained from the monomer administration group with those of the FSR administration group, drug–drug interaction of coexistent components in FSR on the stability of BL and B was discussed.

Results: The degradation of BL and B was both pH- and temperature-dependent with their correlation coefficents for first-order kinetics equation larger than 0.99, and acidic environment (pH 2–4.5), lower temperature (<4 °C) and acidic antioxidant (e.g. vitamin C) were conducive to stabilize B and BL. Furthermore, coexistent components in FSR were proved to have function on inhibiting the degradation of BL and B in our study for the first time, which was characteristic of prolonging their biological half-life (t_1/2) significantly, e.g., from 2.89 h to indefinite for BL (pH 6.8, 25 °C), from 2.63 h to 4.48 h for B (pH 6.8, 25 °C) and so on. Antioxidant of Na₂SO₃ could inhibit the degradation of BL with t_1/2 increasing from 1.8 h to 3.5 h, but aggravate the bio-transformation of B with t_1/2 decreasing from 0.92 h to 0.29 h. Our research proved that BL monomer, and BL and B in FSR form could be stabilized enough to meet the requirement of biological quantitative analysis under the protection of coexistent components in FSR.

Discussion and conclusion: The results obtained indicated that the stability of BL and B was affected not only by its environmental parameters, but also by the coexistent components in the effective total flavonoids fractions.

Keywords:

• Degradation
• drug–drug interaction
• HPLC

Disclosure statement

The authors report that they have no conflicts in interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This research work was financially supported by the Science and Technology Planning Project of Guangdong province [No. 2016A020226031] and the Program of Science and Technology of Guangzhou [No: 201607010334] of Guangdong Provincial Science and Technology Department.