Determination of levamlodipine concentration by LC-MS/MS and its chiral transformation potential in human plasma

Objective To determine S-(-)-amlodipine level in human plasma by LC-MS/MS method, and to investigate its chiral transformation potential in healthy male volunteers. Methods The separation of amlodipine was performed by CHIRAL-AGP analytical column (150. 0 mm × 4. 0 mm, 5 μm) with 10 mmol/L acetate buffer (pH 4. 38)-2-propanol (98 = 2, V/V) as the mobile phase and chlordiazepoxide as the internal standard. The plasma S-(-)-amlodipine was extracted with solid phase extraction in ten healthy male volunteers at different lime points after oral test (2. 5 mg). Atmospheric-pressure chemical ionization (APCI) and multiple reaction monitoring (MRM) were used with positive ion scans, and the mass transition pairs of m/z 409.0-→237. 9 and m/z 300. 0-→282. 0 were used to detect amlodipine and internal standard, respectively. Results The linear calibration curve of each enantiomer of amlodipine showed excellent correlation over the range of 0. 1031 ptg/L (20. 62 jig/ L(r=0. 999 8, r=0. 999 7). The absolute recovery was more than 70. 0%, the relative recoveries were 85. 0%-115. 0% < and intra-run and inter-run relative standard deviation (RSD) were less than 15. 0%. No R-(-)-amlodipine was detected in the plasma of ten healthy male volunteers at different time points after single oral test. The main pharmacokinetic parameters of S-(-)-amlodipine in healthy male volunteers were as follows;ti/a was (42. 77 + 8. 08) h, Cma was (3. 06 + 0. 51) j→g/L, tmnx was (6.3+1.0) h. MRT was (69.25 + 8.04) h. AUCo-i« was (176.20+31.89) h •,xg • L '. and AUC, was (197. 92 + 37. 54) h • jxg • L. Conclusion The present method is highly selective, sensitive, accurate and with no endogenous interference for pharmacokinetic study. R-(+)-amlodipine is not found in the plasma, indicating that there is no chiral transformation in healthy male volunteers.