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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. Highlights • LC-MS/MS methods were firstly developed and validated for assaying urinary tylerdipine and its two metabolites in human. • The methods were applied to evaluate urinary excretion of tylerdipine and its two metabolites in healthy Chinese subjects. • The urinary excretion of the two metabolites accounted for 11.7%, while little tylerdipine was recovered in human urine. [ABSTRACT FROM AUTHOR]

Sitafloxacin is a new fluoroquinolone antimicrobial agent with high activity. In this article, we reported a simple, rapid and specific LC–MS/MS method for accurate determination of sitafloxacin concentrations in human urine from healthy volunteers in detail. A two-step dilution method for the analysis of sitafloxacin in human urine using LC coupled to positive MS/MS has been developed and validated according to US FDA guidelines and Chinese State Food and Drug Administration (CFDA) guidelines for the validation of bioanalytical methods. The method uses 50 μL of urine and covers a working range from 0.025 to 20 μg/mL with a LLOQ of 0.025 μg/mL. This new LC–MS/MS assay is sensitive and specific. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to develop a rapid and sensitive method for the simultaneous quantification of metronidazole (MEZ), tinidazole (TNZ), ornidazole (ONZ) and morinidazole (MNZ) in human saliva. A reversed-phase high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection at 318nm was carried out on a C18 column, using a mixture of potassium dihydrogen phosphate buffer, acetonitrile, and methanol (55:15:30, v/v/v) as a mobile phase with a flow rate of 1.0ml/min. The saliva samples (100μl) were firstly deproteinized by precipitation with methanol (400μl), after which they were centrifuged and the supernatants were directly injected into the HPLC system. This method produced linear responses in the concentration ranges of 25.2–5040.0, 23.9–4790.0, 25.4–5080.0, 25.0–5000.0ng/ml with detection limits of 6.0, 17.6, 10.0 and 11.3ng/ml for MEZ, TNZ, ONZ and MNZ (S/N=3), respectively. The methods were validated in terms of intra- and inter-batch precision (within 7.3% and 9.1%, respectively), accuracy, linearity, recovery and stability. The study proved that HPLC is both sensitive and selective for the simultaneous quantification of MEZ, TNZ, ONZ and MNZ in human saliva using a single mobile phase. [Copyright &y& Elsevier]

Abstract: A specific and sensitive liquid chromatography electrospray ionization tandem mass spectrometric (LC–ESI-MS/MS) method for quantitative determination of sertaconazole in human plasma was developed. The analysis was performed and validated in positive ion multiple reactions monitoring mode using loratadine as an internal standard (IS). Sample preparation involved one-step liquid–liquid extraction using ether–dichloromethane (80/20, v/v). Sertaconazole and IS was separated on a C18 column using isocratic elution with a mobile phase of methanol: 0.2% formic acid aqueous solution (70:30, v/v,) at the flow rate of 0.2mL/min. The transition monitored were m/z 439 [M+H]+ → m/z 181 for sertaconazole and m/z 383[M+H]+ → m/z 337 for IS. The lower limit of quantification was 0.1ng/mL based on 500μL of plasma, and no interferences were detected in chromatograms. Calibration curve was linear over the range of 0.1–10ng/mL, and correlation coefficients were 0.999. Intra- and inter-day assay variations were <10%, and the accuracy values were between −0.4% and 9.0% relative error (RE). The extraction recoveries ranged from 60% to 70% across the calibration curve range. The described method provides a sensitive analytical tool to determine sertaconazole in plasma, and was successfully applied to a pharmacokinetic study in 10 healthy human subjects after administration of 300mg vaginal suppository formulation of sertaconazole nitrate. [Copyright &y& Elsevier]