Simultaneous determination of amoxicillin and ambroxol in human plasma by LC-MS/MS: validation and application to pharmacokinetic study.
A rapid, simple and sensitive LC-MS/MS method was developed for simultaneous determination of amoxicillin and ambroxol in human plasma using clenbuterol as internal standard (IS). The plasma samples were subjected to a simple protein precipitation with methanol. Separation was achieved on a Lichrospher C(18) column (150 mm x 4.6mm ID, dp 5 microm) using methanol (containing 0.2% of formic acid) and water (containing 0.2% of formic acid) as a mobile phase by gradient elution at a flow rate of 1.0 mL/min. Detection was performed using electrospray ionization in positive ion multiple reaction monitoring (MRM) mode by monitoring the ion transitions from m/z 365.9-->348.9 (amoxicillin), m/z 378.9-->263.6 (ambroxol) and m/z 277.0-->203.0 (IS). Calibration curves were linear in the concentration range of 5-20,000 ng/mL for amoxicillin, and 1-200 ng/mL for ambroxol, with the intra- and inter-run precisions of <9% and the accuracies of 100+/-7%. The method has been validated and applied to pharmacokinetic studies of compound amoxicillin and ambroxol hydrochloride tablets in healthy Chinese volunteers.
Wen
Aidong
A
Department of Pharmacy, Xijing Hospital of the Fourth Military Medical University, Xi'an 710032, China. adwen-2004@hotmail.com
Hang
Taijun
T
Chen
Suning
S
Wang
Zhirui
Z
Ding
Likun
L
Tian
Yun
Y
Zhang
Meng
M
Xu
Xinxin
X
D000551:Ambroxol / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D000658:Amoxicillin / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D000900:Anti-Bacterial Agents / Q000097:blood*; D019540:Area Under Curve; D044466:Asian People; D002138:Calibration; D002853:Chromatography, Liquid / Q000295:instrumentation / Q000379:methods*; D018592:Cross-Over Studies; D004338:Drug Combinations; D004355:Drug Stability; D005100:Expectorants / Q000032:analysis* / Q000493:pharmacokinetics; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D015394:Molecular Structure; D016032:Randomized Controlled Trials as Topic; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013607:Tablets / Q000032:analysis; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013696:Temperature; D013997:Time Factors
D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D005100:Expectorants; D013607:Tablets; D000551:Ambroxol; D000658:Amoxicillin