Abstract

Objectives: Propofol has become the preferred anesthetic in recent years due to its desirable pharmacologic properties. However, propofol possesses a very narrow therapeutic window between the favorable clinical effect and potentially lethal toxicity, therefore, a rapid, simplified, and sensitive liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry (LC-APCI-MS/MS) method is presented in this study for the quantification of propofol in human plasma using the isotope-labeled internal standard (IS) of propofol-d17, and then applied in a bioequivalence study.
Materials and methods: Sample preparation was accomplished through simple one-step precipitation of plasma protein with acetonitrile. Chromatographic separation was acquired on an ACE Excel 3 Super C₁₈ column (2.1 × 50 mm, 3 µm) using gradient elution at a flow rate of 0.5 mL/min. The MS detection was achieved in the negative ion APCI by multiple reaction monitoring (MRM) mode using the transitions of m/z 177.2 → 161.0 for propofol and m/z 194.2 → 174.2 for IS, respectively. 30 healthy Chinese subjects were enrolled in the open-label, randomized, two-period, two-sequence, cross-over bioequivalence study after single-dose intravenous administration of propofol medium-chain triglyceride and long-chain triglyceride (MCT/LCT).
Results: The current method was precise and accurate at a linearity range of 4.00 – 1,000 ng/mL without severe interference from the plasma matrix. The inter- and intra-batch precision (2.3 to 15.8%) and accuracy (–4.4 to 3.0%), IS-normalized matrix effect (coefficient of variation ≤ 4.6%), extraction recovery (107.1 – 117.1%), stability (coefficient of variation ≤ 8.0%), and dilution integrity were all within the acceptable range. The 90% confidence intervals (CIs) of the ratios of the geometric means (test/reference) were 86.44 – 104.88% for C_max, 96.30 – 104.52% for AUC_0–t, and 96.56 – 105.05% for AUC_0–∞, which were all within the predefined bioequivalence range of 80 – 125%. Besides, both propofol MCT/LCT preparations were well tolerated in healthy Chinese subjects, and there were no serious adverse events during the study.
Conclusion: The method is more simplified and sensitive than the previously reported modes of propofol detection. The two propofol MCT/LCT preparations were considered to be bioequivalent.

Author Details

Authors

• Ling Tang^{1, 3}
• KeLi Wang³
• Chun Peng^{1, 3}
• XuanWei Li^{2, 3}
• Le Li^{2, 3}
• Yan Wang¹
• and Li Ding^{2, 3}

Departments

• ¹ College of Pharmacy and Chemistry, Dali University, Dali,
• ² Department of Pharmaceutical Analysis, China Pharmaceutical University, and
• ³ Nanjing Clinical Tech Laboratories Inc., Nanjing, China

Address


Yan Wang, MD, PhD

College of Pharmacy and Chemistry, 
Dali University
Dali, 671000, China
Email: [email protected]

Citation