Enhanced HPLC‐MS/MS method for the quantitative determination of the co‐administered drugs ceftriaxone sodium and lidocaine hydrochloride in human plasma following an intramuscular injection and application to a pharmacokinetic study

Abstract

A sensitive HPLC-MS/MS method was established for the quantification of ceftriaxone sodium (CFT) and lidocaine HCl (LDC) in human plasma utilizing cefixime (CFX) and tadalafil (TDA) as internal standards. The analytes were extracted from human plasma by protein precipitation using acetonitrile. Chromatographic separation was performed on Kinetex C (50.0 × 4.6 mm, 5 μm particle size) column with methanol-0.01 M ammonium acetate pH 6.4 (70: 30, v/v) as mobile phase. Multiple reaction monitoring involving the transitions 555.10 → 396.20, 235.20 → 86.00, 454.20 → 284.80 and 390.20 → 268.20 was utilized to quantify CFT, LDC, CFX and TDA, respectively, using a triple quadrupole mass spectrometer which was operated in positive ion mode. The method revealed linearity in the concentration range of 3.0-300.0 μg/mL for CFT and 3.0-300.0 ng/mL for LDC. The validation of the method was achieved in accordance to the US Food and Drug Administration guidelines. A pharmacokinetic study was performed on healthy Egyptian volunteers after intramuscular injection of sterile ceftriaxone sodium (1 g CFT dissolved in 3.5 mL of 1% LDC) after approval from the ethics committee. The pharmacokinetic parameters were: C 141.15 ± 39.84 (μg/mL) and 55.02 ± 9.36 (ng/mL); t (h) 2.50 ± 0.50 and 1.5 ± 0.50; t (h) 7.30 ± 2.98 and 4.23 ± 1.96; and K (h ) 0.10 ± 0.04 and 0.20 ± 0.13 for CFT and LDC, respectively.

Simultaneous Determination of Tinidazole and Lidocaine in Pharmaceutical Preparations by HPLC with Photodiode Array Detection

“…In the literature research, no study was found regarding the simultaneous determination of TIN and LID in pharmaceutical preparations. It was determined that HPLC [14,15] and HPLC/MS/MS [16,17] methods were generally used in studies conducted separately for both active ingredients.…”

A Review of Methods for Removal of Ceftriaxone from Wastewater

“…Literature shows a higher proportion of the usage of HPLC in the analysis of ceftriaxone in the aqueous and biological samples [ 14 ]. The methods studied for the analysis of ceftriaxone include high-performance liquid chromatography coupled with mass spectrometry detection (HPLC-MS) [ 14 , 71 , 72 ], high-performance liquid chromatography with detection by ultraviolet (HPLC-UV) [ 14 , 73 , 74 , 75 , 76 ], and high-performance liquid chromatography coupled with sequential mass spectrometry (HPLC-MS/MS) [ 14 , 77 , 78 , 79 , 80 , 81 ]. The referred methods studied for the analysis of ceftriaxone also include ultra-performance liquid chromatography with detection by ultraviolet (UPLC-UV) [ 14 , 82 ] and ultra-performance liquid chromatography coupled with sequential mass spectrometry (UPLC-MS/MS) [ 49 , 83 , 84 ].…”

Determination of ceftriaxone in human plasma using liquid chromatography–tandem mass spectrometry

“…The objective of this study was to develop and validate an accurate and sensitive bioanalytical method for ceftriaxone determination in low volume human plasma using LC-MS/MS. Only a few research publications have reported using LC-MS/MS for ceftriaxone determination in human biological samples [13][14][15][16] . Thus, this will be one of the first methods for ceftriaxone determination by LC-MS/MS and an alternative option to the already published methods.…”