Introduction

Fenofibrate is a drug newly listed in the 18th edition of the Japanese Pharmacopoeia (JP) and is used in the treatment of dyslipidemia (hyperlipidemia), which causes atherosclerosis and myocardial infarction. This drug reduces LDL cholesterol (bad cholesterol) levels and increases HDL cholesterol (good cholesterol) levels by promoting the breakdown of triglycerides and inhibiting the synthesis of cholesterol.

In this report, we present the results of a system suitability evaluation for purity tests and assays of fenofibrate in accordance with the Japanese Pharmacopoeia, 18th Edition.

LC-4500 series HPLC system

Experimental

Instruments
Pump:  PU-4580
Degassing unit:  DG-4580
Autosampler:  AS-4550
Column oven:  CO-4060
Detector:    UV-4570

Conditions
Column:   Unifinepak C18 (4.6 mmI.D. x 150 mmL, 5 µm)
Eluent :   Acetonitrile/20 mM sodium dihydrogen phosphate (adjusted to pH 3.0 with phosphoric acid) (70/30)
Flow rate:   1.4 mL/min (adjusted so that the retention time of   fenofibrate is approximately 8 minutes)
Column temp.:  40 ºC
Wavelength:    286 nm
Injection volume:   20 µL
Standard:   Fenofibrate (The dissolving and diluting solvent is a   mixture of acetonitrile and water (7:3).)
Internal standard:  4-Chlorobenzophenone (The dissolving and diluting   solvent is a mixture of   acetonitrile and water (7:3).)

Structure

Fenofibrate

Keywords

Japanese Pharmacopoeia, fenofibrate, UV detector

Results

An overview of the system suitability for purity tests and assays of fenofibrate is shown in Table 1.

Table 1   Overview of system suitability for purity tests and assays of fenofibrate

(1) Purity

Figure 1 shows the results of the detectability test. The ratio of the fenofibrate peak area for the diluted solution (0.12 mg/L) to that for the standard solution (0.6 mg/L) was 20.1 %, which met the criterion of 15–25 %.

Fig.1   Chromatogram of fenofibrate for the    detectability test (0.6 mg/L, 0.12 mg/L)

Figure 2 shows the results of the system performance test. 4-chlorobenzophenone and fenofibrate eluted in that order, and the resolution for the peaks was 15.4, which met the criterion of ≥10.

Fig. 2   Chromatogram of 4-chlorobenzophenone   and  fenofibrate for system performance   (0.8 mg/L each)

     Figure 3 shows chromatograms of fenofibrate standard solutions, and Table 2 shows the results for peak area reproducibility based on the measured system reproducibility. The relative standard deviation of the peak area was 0.19 %, which met the criterion of ≤5.0 %.

Fig. 3   Chromatograms of fenofibrate standard solutions (0.6 mg/L, n = 6)

Table 2   Fenofibrate peak area reproducibility (n = 6)

(2)Assay

Figure 4 shows chromatograms of a standard solution of fenofibrate containing the internal standard, 4-chlorobenzophenone (40 mg/L and 44 mg/L, respectively), and Table 3 shows the reproducibility of the fenofibrate to internal standard peak area ratio. 4-Chlorobenzophenone and fenofibrate eluted in that order. The resolution for the peaks was 15.2 (criterion: ³10), and the relative standard deviation of the peak area ratio was 0.04 % (criterion: ≤1.0 %), which both met the specified criteria.

Fig. 4   Chromatograms of 4-chlorobenzophenone and fenofibrate standard solution (44 mg/L and 40 mg/L, respectively, n = 6)

Table 3   Fenofibrate peak area ratio    reproducibility (n = 6)

*Fenofibrate/4-chlorobenzophenone

Conclusion

We evaluated the system suitability for purity tests and assays of fenofibrate, which is newly listed in the 18th edition of the Japanese Pharmacopoeia. As shown in Table 4, all of the evaluation results met the specified criteria for the Japanese Pharmacopoeia.

Table 4   Results of system suitability evaluation for purity tests and assays of fenofibrate