Conversion investigation for lovastatin and its derivatives by HPLC.
A high-performance liquid chromatography (HPLC) method was developed for the separation of lovastatin (LT) and its derivatives. The conversion of LT and its derivatives in alkaline or acidic solution in different storage times was also investigated by HPLC. The results showed that LT was present in different forms: as a lactone, as lovastatin acid (LA), and as its methyl ester (LM) under acidic condition. Well-resolved peaks of three forms compounds of lovastatin were separated on a Symmetry C(18) column (4.6 x 250 mm i.d., particle size 5 mum) using acetonitrile-water (77:23, v/v) as the mobile phase at pH 3.0. The retention time of LA, LT, LM was 6.41 +/- 0.25 min, 8.89 +/- 0.25 min, 9.73 +/- 0.25 min, respectively. LT only converted to LA when LT was treated with 0.1 M NaOH. Under the acidic condition, with the increase of storage time, LT converted to LA, following LA would be transformed to LT and LM. Apparently, containing high concentrations of methanol in acidic methanol solutions might facilitate the conversion of LA to LM, and conversion of LT, LA, and LM would almost reach equilibrium after 60 h. The concentration of methanol and the storage time would also change the form of the LT when LA, LT, and LM were extracted by methanol-water in acidic condition. So the determination and separation of LA and LT should possibly exclude methanol in acidic condition.
Huang
Zhibing
Z
Sino-Germany Joint Research Institute, State Key Laboratory of Food Science, Nanchang University, Nanchang 330047, China.
Xu
Yang
Y
Li
Yanping
Y
Wang
Yanhua
Y
D000097:Acetonitriles / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006851:Hydrochloric Acid / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D016014:Linear Models; D008148:Lovastatin / Q000031:analogs & derivatives / Q000737:chemistry; D000432:Methanol / Q000737:chemistry; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012972:Sodium Hydroxide / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization
D000097:Acetonitriles; D012972:Sodium Hydroxide; D008148:Lovastatin; D006851:Hydrochloric Acid; D000432:Methanol; C032159:acetonitrile