Development and validation of an HPLC-MS/MS assay for the quantitative analysis of remimazolam in critically ill patients

Chen, Jingchun1; Wu, Meifen2; Xiao, Yumei3; Chen, Dong4; Wang, Yirong1,2; Bai, Yunpeng5; Wang, Xipei6,7; Hu, Linhui5,8; Huang, Rongrong9; Chen, Chunbo1,10,11; Lai, Weihua1,12

2023-10-01

10.1016/j.ijms.2023.117120

INTERNATIONAL JOURNAL OF MASS SPECTROMETRY   Impact Factor & Quartile

1387-3806

1873-2798

Remimazolam is a novel benzodiazepine which is commonly used in procedural sedation, but its pharmacokinetics in critically ill patients have not yet been unequivocally clarified. A high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method was established and validated for the determination of the remimazolam concentration in human plasma. The plasma sample extraction method was protein precipitation. A triple quadrupole mass spectrometer equipped with an electrospray ionization source and multiple reaction monitoring was used for mass spectrometry analysis. The analytes were isolated on an ACQUITY UPLC BEH C18 column with the mobile phase A (10 mM ammonium acetate in water containing 0.2% formic acid) and mobile phase B (acetonitrile) under a gradient program. The retention time of the analyte and IS were 2.0 and 1.4 min, respectively. The linear range for quantitative analysis of remimazolam was 1.0-1000 ng/mL and the extraction recovery rate was 97.3%-99.3%. According to the Chinese Pharmacopoeia and the ICH Harmonized Guidelines for Biological Analysis Method Validation, this approach has been validated in terms of selectivity, accuracy, precision, carryover, dilution integrity, matrix effects and stability. In a population pharmacokinetic study of remimazolam that targeted patients in intensive care units, the HPLC-MS/MS method was successfully applied to the quantitative measurement of remimazolam concentrations in human plasma. This method has the advantages of simplicity of operation, reliability, and sensitivity.

Remimazolam HPLC-MS/MS Quantitative analysis Method validation Human plasma

SCI

English

Corresponding

ICU Sedation and Analgesia Special Project of China International Medical Foundation[200221115835503] ; null[Z-2017-24-2028-03] ; null[2021A1515220085]

Physics ; Spectroscopy

Physics, Atomic, Molecular & Chemical ; Spectroscopy

WOS:001059479200001

ELSEVIER

CHEMISTRY

Web of Science

1.South China Univ Technol, Sch Biol & Biol Engn, Guangzhou 510006, Peoples R China
2.Southern Med Univ, Guangdong Prov Peoples Hosp, Guangdong Acad Med Sci, Dept Intens Care,Unit Cardiovasc Surg, Guangzhou 510080, Peoples R China
3.Maoming Peoples Hosp, Dept Neurocrit Care Unit, Maoming 525000, Peoples R China
4.South China Univ Technol, Sch Med, Guangzhou 510006, Peoples R China
5.Maoming Peoples Hosp, Ctr Sci Res, Maoming 525000, Peoples R China
6.Southern Med Univ, Guangdong Prov Peoples Hosp, Guangdong Acad Med Sci, Res Ctr Med Sci, Guangzhou 510080, Peoples R China
7.Southern Med Univ, Guangdong Prov Peoples Hosp, Guangdong Acad Med Sci, Guangdong Prov Key Lab Clin Pharmacol, Guangzhou 510080, Peoples R China
8.Maoming Peoples Hosp, Dept Crit Care Med, Maoming 525000, Peoples R China
9.Yichang Humanwell Pharmaceut Co Ltd, Yichang, Peoples R China
10.Maoming Peoples Hosp, Dept Emergency Med, Maoming 525000, Peoples R China
11.Southern Univ Sci & Technol, Clin Med Coll 2, Affiliated Hosp 1, Dept Crit Care Med,Shenzhen Peoples Hosp,Jinan Uni, Shenzhen 518000, Peoples R China
12.Southern Med Univ, Guangdong Prov Peoples Hosp, Guangdong Acad Med Sci, Dept Pharm, Guangzhou 510080, Peoples R China

Chen, Jingchun,Wu, Meifen,Xiao, Yumei,et al. Development and validation of an HPLC-MS/MS assay for the quantitative analysis of remimazolam in critically ill patients[J]. INTERNATIONAL JOURNAL OF MASS SPECTROMETRY,2023,492.

Chen, Jingchun.,Wu, Meifen.,Xiao, Yumei.,Chen, Dong.,Wang, Yirong.,...&Lai, Weihua.(2023).Development and validation of an HPLC-MS/MS assay for the quantitative analysis of remimazolam in critically ill patients.INTERNATIONAL JOURNAL OF MASS SPECTROMETRY,492.

Chen, Jingchun,et al."Development and validation of an HPLC-MS/MS assay for the quantitative analysis of remimazolam in critically ill patients".INTERNATIONAL JOURNAL OF MASS SPECTROMETRY 492(2023).