Simultaneous analysis of drugs administered to lung‐transplanted patients using liquid chromatography–tandem mass spectrometry for therapeutic drug monitoring

Abstract

Several drugs are administered to lung‐transplanted patients, which are monitored using therapeutic drug monitoring (TDM). Therefore, we developed and validated a liquid chromatography–tandem mass spectrometry method to simultaneously analyze immunosuppressive drugs such as mycophenolic acid, antifungal drugs such as voriconazole and itraconazole, and its metabolite hydroxyitraconazole. Chromatographic separation was achieved using a C18 column and gradient flow of mobile phase comprising 20 mM aqueous ammonium formate and 20 mM ammonium formate‐methanol solution. A simple protein precipitation treatment was performed using acetonitrile/methanol and mycophenolic acid‐2H3, voriconazole‐2H3, itraconazole‐2H4, and hydroxyitraconazole‐2H4 as internal standards. The linearity ranges of mycophenolic acid, voriconazole, itraconazole, and hydroxyitraconazole were 100–20,000, 50–10,000, 5–1000, and 5–1000 ng/mL, respectively. The retention time of each target was less than 2 min. The relative errors in intra‐ and inter‐day were within ±7.6%, the coefficient of variation was 8.9% or less for quality control low, medium, and high, and it was 15.8% or less for lower limit of quantitation. Moreover, the patient samples were successfully quantified, and they were within the linear range of measurements. Therefore, our new method may be useful for TDM in lung‐transplanted patients.

Cutting‐edge LC–MS/MS applications in clinical mass spectrometry: Focusing on analysis of drugs and metabolites

“…This technique has the advantage of allowing simultaneous analysis of multiple drugs. In some cases, drugs used in clinical practice for combination therapy have been quantified simultaneously (Takasaki et al, 2021). In addition, when a large number of drugs are available, often, a simultaneous measurement method is constructed using LC–MS/MS, instead of a single measurement system for each drug (Hirasawa et al, 2021; Sato, Shigeta, et al, 2021; Sato, Suzuka, et al, 2021; Takasaki, Tanaka, et al, 2018).…”

“…In this analytical method, although the quantitative concentration ranges were different, the method was optimized with the same is‐CID value (95 V of Qarray bias) because of the difference in ionization efficiency. In addition, the developed method can be readily applied to clinical practice (Takasaki et al, 2021). In the future, it is expected that MS sensitivity adjustment methods such as is‐CID will be increasingly used in the development of analytical methods for such combination therapies.…”

Development of a Highly Sensitive and Rapid Liquid Chromatography–Tandem Mass Spectrometric Method Using a Basic Mobile Phase Additive to Determine the Characteristics of the Urinary Metabolites for Niemann–Pick Disease Type C

“…Linearity, Calibration Curves, and Matrix Effects Generally, calibration curves for drugs that are not normally contained are generated by adding standard solutions to the sample matrix. [59][60][61][62][63] However, when analytes are endogenous compounds that are found in all participants, an alternative approach must be selected. 64) In this study, we prepared calibration curves using water as a surrogate matrix based on previous methods.…”