Rapid and Sensitive LC-MS/MS Assay for Quantitation of Letrozole Using Solid-Phase Extraction from Human Blood Plasma and Its Application to Pharmacokinetic Studies

Simultaneous quantification of palbociclib, ribociclib and letrozole in human plasma by a new LC-MS/MS method for clinical application

“…To deepen the knowledge about the interindividual variation in pharmacokinetics and relationship with patient outcome, large prospective clinical studies are needed, as well as more validated bioanalytical methods to support them. At the best of our knowledge, for the quantification of these drugs in human plasma, only one LC-UV method was published for PALBO [8], two LC-MS/MS methods were published for RIBO [9,10], while several LC-MS/MS assays [11][12][13][14][15][16] and one LC-UV method [17] were reported for LETRO. Recently, a LC-MS/ MS method was also proposed for the quantification of the CDKIs in human plasma [18] but not for the simultaneous determination of LETRO.…”

SPE–UPLC–MS/MS assay for determination of letrozole in human plasma and its application to bioequivalence study in healthy postmenopausal Indian women

“…A standard solution (1000 ng/mL) of LTZ and LTZ-d4 was directly infused into the MS using ESI as the ionization source. The mass spectrometer was tuned in both positive and negative ionization modes to obtain consistent and abundant product ions in the mass range of 100–340 amu, based on previous studies [6] , [7] , [9] , [10] , [11] . Due to the presence of tertiary nitrogen groups in LTZ the response in the positive ionization mode was greater than that in the negative mode.…”

“…To establish a linear concentration range from 0.1 to 100 ng/mL, it was essential to optimize an efficient extraction protocol to obtain quantitative and precise recovery of LTZ and LTZ-d4 with minimal matrix effect. As all three conventional extraction methodologies, namely protein precipitation (PP) [8] , [10] , liquid-liquid extraction (LLE) [7] , [12] and SPE [6] , [9] , [11] , have been used previously, a systematic study was undertaken to optimize the best extraction conditions with all three approaches. As the PP has the advantage of simplicity and speed of analysis, the initial attempts were done with methanol and acetonitrile as protein precipitants.…”

“…Several methods are reported for the determination of LTZ as a single analyte [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] , together with its inactive metabolites [13] , [14] and with other drugs like tamoxifen and anastrozole [15] in different biological matrices. Mainly liquid chromatography with UV [4] , [5] , [12] , fluorescence [3] , [14] or mass spectrometry [6] , [7] , [8] , [9] , [10] , [11] , [13] , [15] detection has been used for the quantification of LTZ in various matrices like human urine, rat plasma and human plasma. All previous methods based on liquid chromatography with mass spectrometric detection have sensitivity less than 0.2 ng/mL and chromatographic analysis time ranging from 3.0 to 16.0 min.…”

“… Linear range (ng/mL) Plasma volume (µL) Extraction procedure; internal standard Mean recovery (%) Chromatographic run time (min); retention time (min) Application; Incurred sample reanalysis Ref. 1 0.20–100 250 LLE with methyl tert-butyl ether; LTZ-d4 65.7 3.0; 1.25 Pharmacokinetic study with 2.5 mg LTZ in 72 healthy volunteers under fasting & fed condition; – [7] 2 0.40–50 100 PP with methanol-water and acetonitrile; LTZ-d4 90.5 4.0; 2.7 Clinical pharmacokinetic study with 2.5 mg LTZ in 20 healthy, post-menopausal Chinese women; % change within 20% [8] 3 0.25–100 500 SPE on SOLA cartridges; olanzapine 87.1 3.0; 2.043 Pharmacokinetic study with 2.5 mg LTZ in 32 healthy, post-menopausal women; – [9] 4 1.0–60 50 PP with methanol; anastrozole – 5.5; 3.81 Analysis of samples from patients treated with 2.5 mg/day LTZ; – [10] 5 a 5.7–428 150 SPE on BondElut C 18 96-well plates; LTZ-d4 98.5 4.75; 3.86 Quantification of LTZ and its metabolites in the plasma samples of 20 post-menopausal patients with early breast cancer receiving a daily dose of 2.5 mg LTZ; – [14] 6 b 10–300 1000 SPE on Strata X-C; bunitrolol 49.0 16; 8.0 Analysis of plasma samples of 310 breast cancer patients undergoing anti-estrogen therapy; – [15] 7 c 0.10–100 100 SPE on Orochem DVB-LP cartridge; LTZ-d4 ...…”