Quantification of strontium in human serum by ICP-MS using alternate analyte-free matrix and its application to a pilot bioequivalence study of two strontium ranelate oral formulations in healthy Chinese subjects

• Published in: Journal of trace elements in medicine and biology 2015-01, Vol.29, p.69-74
• Main Authors: Zhang, Dan, Wang, Xiaolin, Liu, Man, Zhang, Lina, Deng, Ming, Liu, Huichen
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adult; Alternate matrix; Asian Continental Ancestry Group; Bioequivalence study; Calibration; Chemistry, Pharmaceutical; Health; Human serum; Humans; ICP-MS; Male; Pilot Projects; Reproducibility of Results; Spectrophotometry, Atomic - methods; Strontium; Strontium - blood; Strontium - pharmacokinetics; Therapeutic Equivalency; Thiophenes - administration & dosage; Thiophenes - blood; Thiophenes - pharmacokinetics; Young Adult
• ISSN: 0946-672X; 1878-3252
• DOI: 10.1016/j.jtemb.2014.06.008

•An ICP-MS method for quantification of exogenous Sr from the drug in human serum was developed and thoroughly validated.•Direct dilution for sample preparation and short analytical cycle time allowed high sample throughput.•Using distilled water as alternate analyte-free matrix avoided the influence of endogenous Sr in serum on quantification.•The method was applied to a pilot BE study of a new oral formulation of strontium ranelate and the brand-name drug.•Parallel design might be better for the BE study of oral formulations of strontium ranelate than crossover design. A rapid, sensitive and accurate ICP-MS method using alternate analyte-free matrix for calibration standards preparation and a rapid direct dilution procedure for sample preparation was developed and validated for the quantification of exogenous strontium (Sr) from the drug in human serum. Serum was prepared by direct dilution (1:29, v/v) in an acidic solution consisting of nitric acid (0.1%) and germanium (Ge) added as internal standard (IS), to obtain simple and high-throughput preparation procedure with minimized matrix effect, and good repeatability. ICP-MS analysis was performed using collision cell technology (CCT) mode. Alternate matrix method by using distilled water as an alternate analyte-free matrix for the preparation of calibration standards (CS) was used to avoid the influence of endogenous Sr in serum on the quantification. The method was validated in terms of selectivity, carry-over, matrix effects, lower limit of quantification (LLOQ), linearity, precision and accuracy, and stability. Instrumental linearity was verified in the range of 1.00–500ng/mL, corresponding to a concentration range of 0.0300–15.0μg/mL in 50μL sample of serum matrix and alternate matrix. Intra- and inter-day precision as relative standard deviation (RSD) were less than 8.0% and accuracy as relative error (RE) was within ±3.0%. The method allowed a high sample throughput, and was sensitive and accurate enough for a pilot bioequivalence study in healthy male Chinese subjects following single oral administration of two strontium ranelate formulations containing 2g strontium ranelate.