Bioanalytical Method Development and Validation of Memantine in Human Plasma by High Performance Liquid Chromatography with Tandem Mass Spectrometry: Application to Bioequivalence Study

Abstract

A simple, sensitive, and rapid HPLC-MS/MS method was developed and validated for quantitative estimation of memantine in human plasma. Chromatography was performed on Zorbax SB-C18 (4.6 × 75 mm, 3.5 μm) column. Memantine (ME) and internal standard Memantine-d6(MED6) were extracted by using liquid-liquid extraction and analyzed by LC-ESI-MS/MS using multiple-reaction monitoring (MRM) mode. The assay exhibited a linear dynamic range of 50.00–50000.00 pg/ml for ME in human plasma. This method demonstrated an intra- and interday precision within the range of 2.1–3.7 and 1.4–7.8%, respectively. Further intra- and interday accuracy was within the range of 95.6–99.8 and 95.7–99.1% correspondingly. The mean recovery of ME and MED6 was 86.07 ± 6.87 and 80.31 ± 5.70%, respectively. The described method was successfully employed in bioequivalence study of ME in Indian male healthy human volunteers under fasting conditions.

Pharmacokinetic Properties of Memantine after a Single Intraperitoneal Administration and Multiple Oral Doses in Euploid Mice and in the Ts65Dn Mouse Model of Down's Syndrome

“…There have been a few published methods for the determination of the concentration of memantine in blood and tissues [22][23][24][25][26][27][28][29]. Based on these published reports and our expertise, we developed a unique procedure for measuring memantine concentration in blood and tissues using commonly found GC/MS.…”

Review of the validated HPLC and LC‐MS/MS methods for determination of drugs used in clinical practice for Alzheimer's disease

“…Typically the biological matrix was alkalinized before the pre‐column derivatization step or extraction step (Suckow et al ., ; Almeida et al ., ; Shuangjin et al ., ; Liu et al ., , ; Pan et al ., ; Zarghi et al ., ; Konda et al ., ) except for the method reported by Puente et al . () and Xie et al .…”

Highly Sensitive LC-MS/MS Method for Determinationof Memantine in Rat Plasma: Application to Pharmacokinetic Studies in Rats

“…Similarly, for IS m/z 180.10 precursor ion to the m/z 110.10 was used for quantification purpose. As the earlier publications [6][7][8] have discussed extensively on fragmentation pattern of MEM and the data pertaining to this was not presented here.…”

“…The mean terminal half-life (t ½ ) is around 60-80 h. MEM and its metabolites are primarily eliminated through urine (75-90%) and the remaining recovered through bile and feces. 4,5 Majority of the LC-MS/MS methods have been reported for estimation of MEM in clinical studies [6][7][8][9][10][11][12] and one method to support preclinical study. Among these methods the lowest reported lower limit of quantification (LLOQ) was 0.05 ng/ml using 100 µl plasma.…”

“…Among these methods the lowest reported lower limit of quantification (LLOQ) was 0.05 ng/ml using 100 µl plasma. 6 In a preclinical set up, especially with rodents, only small volumes of blood (~50-100 µl) can be drawn at each time point during pharmacokinetic studies, in contrast to the clinical scenario, where large blood volumes (up to 3-5 ml) can be drawn at each time point. Hence there is a need to develop and validate an LC-MS/MS method using small volume of plasma for quantification of MEM.…”