LC–MS3 Strategy for Quantification of Carbamazepine in Human Plasma and Its Application in Therapeutic Drug Monitoring

Abstract

This study developed a detection method based on the strategy of HPLC/MS3 and verified its suitability by quantifying carbamazepine in human plasma. The high-performance liquid chromatography–tandem mass spectrometry (HPLC/MS3) system was performed using a Shimadzu UFLC XR liquid chromatography and a SCIEX QTRAP® 5500 linear ion trap triple quadrupole mass spectrometer. The specific operation was as follows: the sample protein was firstly precipitated using methanol, then carbamazepine and carbamazepine-D2N15 were separated on an ACQUITY UPLC HSS T3 column using the gradient elution with solvent A (0.1% formic acid) and solvent B (0.1% formic acid in acetonitrile) at a flow rate of 0.25 mL/min. Each sample was run for 7 min. This method was validated for various parameters including accuracy, precision, selectivity, linearity, LLOQ, etc. Only 5 μL of sample plasma could obtain the result of LLOD 0.5 µg/mL. The intra-day and inter-day precision was <8.23%, and accuracy was between −1.74% and 2.92%. This method was successfully used for monitoring the blood concentration of epilepsy patients after carbamazepine treatment.

Solvent bar microextraction based on using deep eutectic solvent and multivariate optimization for simultaneous determination of antidepressant and antiepileptic drugs in biological fluids

“…Several chromatographic instruments have been used to analyze TCAs and/or CBZ in various matrices, including serum, whole blood, urine, and plasma. These instruments include high-performance liquid chromatography with ultraviolet detection (HPLC-UV) [12][13][14][15], gas chromatography (GC) [16][17][18], HPLC-tandem mass spectrometry (MS/MS) [19][20][21], GC-mass spectrometry (MS) [22,23], and capillary electrophoresis (CE) [24,25]. However, analyzing biological fluids directly is often challenging due to their complexity, which can affect the accuracy of the results.…”

Electrochemical Carbamazepine Aptasensor for Therapeutic Drug Monitoring at the Point of Care

“…Carbamazepine (CBZ), marketed in the U.S. under the brand names Tegretol, Tegretol XR, Epitol, and Carbatrol, is an FDA-approved antiseizure and analgesic drug widely used to treat partial seizures with complex symptomatology, tonic-clonic seizures, trigeminal neuralgia, and bipolar disorder. , It is also prescribed to patients with neuromyotonia, schizophrenia, post-traumatic stress disorder, and attention-deficit hyperactivity disorder . CBZ, a tricyclic compound comprising two benzene rings connected by an azepine with a short side chain (236.27 g/mol), acts on the brain and nervous system to control abnormal nerve impulses causing seizures and neurological-derived disorders by blocking ion channels. − Despite all its benefits, it can cause troubling, disabling, and potentially life-threatening complications, which can be difficult to mitigate clinically because the target therapeutic range is extremely narrow (4–12 mg/L; 16.9–50.8 μM) and severe concentration-related toxicity (i.e., combativeness, hallucinations, chorea, coma, and even death) − can occur even within the therapeutic range. Furthermore, pharmacokinetics influence proper dosing when treating multiple diseases and in multidrug regimens, as is common in treating epilepsy .…”

“…Several analytical techniques have been reported to detect CBZ, such as high-performance liquid chromatography, , mass spectrometry (MS), , liquid chromatography coupled with mass spectrometry (LC–MS), , gas chromatography (GC), capillary chromatography, chemiluminescence, and spectrophotometry . These methods require time-consuming pretreatment processes and sophisticated instrumentation with high per-assay costs, relegating them to centralized laboratory-based tests. , Such methods cannot be applied for rapid, point-of-care therapeutic drug monitoring.…”

Comparison of LC-MS3 and LC-MRM Method for Quantifying Voriconazole and Its Application in Therapeutic Drug Monitoring of Human Plasma

“…The MS 3 detection, a scanning mode of Q-Q-Trap tandem mass spectrometry, for both of which the excitation efficiency and the scanning rate (20,000 Da/s) are significantly improved [ 12 , 13 ]. For MS 3 detection, the precursor ions of analyte are firstly selected in Q1 and then fragmented in Q2 to produce ions that are captured in Q3.…”