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 C18 (50.0 � 4.6 mm, 5 ?m 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 ?g/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: Cmax 141.15 � 39.84 (?g/mL) and 55.02 � 9.36 (ng/mL); tmax (h) 2.50 � 0.50 and 1.5 � 0.50; t� (h) 7.30 � 2.98 and 4.23 � 1.96; and Kel (h?1) 0.10 � 0.04 and 0.20 � 0.13 for CFT and LDC, respectively. � 2018 John Wiley & Sons, Ltd.