Determination of clindamycin in human plasma by liquid chromatography-electrospray tandem mass spectrometry: application to the bioequivalence study of clindamycin.
A simple, sensitive and specific liquid chromatography-electrospray tandem mass spectrometry (LC-MS-MS) method for the determination of clindamycin (I) was developed. Both I and verapamil (II, internal standard) were analyzed using a C18 column with a mobile phase of 80% acetonitrile-0.01% trifluoroacetic acid. Column eluents were monitored by electrospray tandem mass spectrometry. Multiple reaction monitoring (MRM) using the parent to daughter combinations of m/z 425-->126 and 455-->165 was used to quantitate I. A limit of quantitation of 0.0500 microgram/ml was found. The assay exhibited a linear dynamic range of 0.0500-20.0 micrograms/ml and gave a correlation coefficient (r2) of 0.998 or better. The chromatographic run time was approximately 2 min. The intra-batch precision and accuracy of the quality controls (QCs, 0.0500, 0.150, 1.50, 15.0 and 20.0 micrograms/ml) were characterized by coefficients of variation (CVs) of 5.13 to 13.7% and relative errors (REs) of -4.34 to 4.58%, respectively. The inter-batch precision and accuracy of the QCs were characterized by CVs of 4.35 to 8.32% and REs of -10.8 to -4.17%, respectively. The method has successfully been applied to the analysis of samples taken up to 12 h after oral administration of 300 mg of I in healthy volunteers.
Yu
L L
LL
Department of Pharmaceutical Technology, Mithra Bioindustry Co., Ltd., Taipei Hsien, Taiwan. mithra2@mithra.com.tw
Chao
C K
CK
Liao
W J
WJ
Twu
T Y
TY
Liu
C M
CM
Yang
T H
TH
Lin
E T
ET
D000900:Anti-Bacterial Agents / Q000097:blood* / Q000302:isolation & purification / Q000493:pharmacokinetics; D002853:Chromatography, Liquid / Q000379:methods*; D002981:Clindamycin / Q000097:blood* / Q000302:isolation & purification / Q000493:pharmacokinetics; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013810:Therapeutic Equivalency
D000900:Anti-Bacterial Agents; D002981:Clindamycin