0

Development and Validation of Two LC-MS/MS Methods to Assay Urinary Tylerdipine Hydrochloride and Its Metabolites in Healthy Chinese Subjects

Mingxue Tao, Sufeng Zhou, Yuanyuan Wang, Lu Wang, Yuqing Zhao, Lijun Xie, Juan Chen, Yun Liu, Hongwen Zhang, Ning Ou, Guangji Wang, Feng Shao, Jiye Aa

J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Oct 1;1096:172-179.

PMID: 30176506

Abstract:

For quantitative assaying tylerdipine hydrochloride, and its two primary metabolites (M2 and M4) in human urine, two sensitive and accurate LC-MS/MS methods were firstly developed and validated, where multiple reaction monitoring (MRM) was applied under positive electrospray ionization mode for tylerdipine and negative electrospray ionization mode for M2/M4, respectively. Urinary proteins were precipitated using acetonitrile, and deuterated isotopes of tylerdipine and M4 ([D5]‑tylerdipine and [D6]-M4) were used as internal standards. Triton X-100, a good surfactant, was used to prevent the adsorption. An Agilent Poroshell 120 column was employed for chromatographic separation of the analytes with the mobile phases of 2 mM ammonium formate solution (containing 0.1% formic acid) and acetonitrile (45:55 for tylerdipine and 75:25 for the M2/M4, v/v). Flow rate was 0.3 mL/min. Calibration curves for tylerdipine, M2 and M4 in urine were linear over the ranges of 0.02-10 ng/mL, 2-1500 ng/mL and 0.5-200 ng/mL, respectively. The precision, accuracy, specificity and stability of two methods all evaluated and achieved the acceptable criteria. The LC-MS/MS methods were successfully applied to assay urinary excretion of tylerdipine and the metabolites in healthy Chinese subjects who orally received a single dose of 20 mg tylerdipine tablet. Generally, the urinary excretion of the two primary metabolites accounted for 11.7% of the total dose of tylerdipine in healthy Chinese subjects, while little tylerdipine was recovered in urine.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP540692-A Ammonium formate solution Ammonium formate solution 540-69-2 Price
qrcode