Abstract��OBJECTIVE To develop a LC-MS method for simultaneously quantifying four anti-tuberculosis drugs [isoniazid(INH)��pyrazinamide(PZA)�� ethambutol(EMB) and rifampicin(RIF)] in human cerebrospinal fluid and to help guide the clinical medication. METHODS The drugs in cerebrospinal fluid were extracted by acetonitrile precipitation, and separated on ZORBAX Bonus-RP column(2.1 mm��150 mm,3.5 ��m) with the mobile phase of aqueous solution(containing 0.1% formic acid)-acetonitrile(containing 0.1% formic acid)(80��20) at a flow rate of 0.25 mL��min-1. Multiple reaction monitoring(MRM) mode was performed combined with electrospray ionization source operating in the positive ionization mode. RESULTS The liner calibration curves of INH��PZA��EMB and RIF were obtained in the concentration range of 20-5 000(r=0.998 6), 120-30 000(r=0.997 7), 20-5 000(r=0.999 4), 60-15 000(r=0.996 2)ng��mL-1, respectively. The intra-and inter-day precision was less than 15% and the absolute recovery was above 75%. This method was successfully applied to analyze the drugs in cerebrospinal fluid from six clinical samples. CONCLUSION The method is rapid, simple, sensitive and accurate, and proved to be suitable for clinical therapeutic drug monitoring.
������,����,���,����,������,����,��С��,������. HPLC-MS/MS�ⶨ���Լ�Һ�������¡�����������Ұ�����������ƽŨ��[J]. �й�ҩѧ��־, 2018, 53(14): 1209-1215.
QIU Wan-cheng, SUN Tao, LI Feng, LI Tao, ZHAO Zhang-yan,YIN Lin, JIA Xiao-fang, ZHANG Li-jun. Simultaneously Quantifying Isoniazid��Pyrazinamide��Ethambutol and Rifampicin in Human Cerebrospinal Fluid by HPLC-MS/MS. Chinese Pharmaceutical Journal, 2018, 53(14): 1209-1215.
ZUMLA A, GEORGE A, SHARMA V, et al. The WHO 2014 global tuberculosis report��further to go[J]. The Lancet Global Health, 2015, 3(1):e10-e2.
[2]
LI Z C, GE Z M, CAI H B, et al. Clinical research progress of drug-resistance of tuberculous meningitis[J]. Prog Mod Biomed(�ִ�����ҽѧ��չ),2016,16(31):6161,6192-6196.
[3]
HEYSELL S K, MOORE J L, PELOQUIN C A, et al. Outcomes and use of therapeutic drug monitoring in multidrug-resistant tuberculosis patients treated in virginia, 2009-2014[J]. Tuberc Respir Dis(Seoul),2015,78(2):78-84.
[4]
TOSTMANN A, MTABHO C M, SEMVUA H H, et al. Pharmacokinetics of first-line tuberculosis drugs in Tanzanian patients[J]. Antimicrob Agents Chemother,2013,57(7):3208-3213.
[5]
SVENSSON E M, MURRAY S, KARLSSON M O, et al. Rifampicin and rifapentine significantly reduce concentrations of bedaquiline, a new anti-TB drug[J]. J Antimicrob Chemother,2015,70(4):1106-1114.
[6]
SRIVASTAVA A, WATERHOUSE D, ARDREY A, et al. Quantification of rifampicin in human plasma and cerebrospinal fluid by a highly sensitive and rapid liquid chromatographic-tandem mass spectrometric method[J]. J Pharm Biomed Anal,2012,70(6):523-528.
[7]
REYNOLDS J, HEYSELL S K. Understanding pharmacokinetics to improve tuberculosis treatment outcome[J]. Expert Opin Drug Metab Toxicol,2014,10(6):813-823.
[8]
VAN HEESWIJK R P, DANNEMANN B, HOETELMANS R M. Bedaquiline: a review of human pharmacokinetics and drug-drug interactions[J]. J Antimicrob Chemother, 2014, 69(9):2310-2318.
[9]
MOHAMED S, RIVA R, CONTIN M. Simple and validated UHPLC-MS/MS analysis of nimodipine in plasma and cerebrospinal fluid of patients with subarachnoid haemorrhage[J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2016,1028:94-99.
[10]
LIU Q H, ZHANG W H. Advances in PK/PD studies of anti-tuberculosis drugs[J]. Chin J Infect Chemother(�й���Ⱦ�뻯����־),2016,16(5):662-666.
[11]
QIN H L,ZHU H,WEI Y,et al. HPLC Fingerprints of Feijiehe Pills[J]. Chin Pharm J (�й�ҩѧ��־), 2016, 51(21):1877-1879.
[12]
PRAHL J K, LUNDQVIST M, BAHL J M, et al. Simultaneous quantification of isoniazid, rifampicin, ethambutol and pyrazinamide by liquid chromatography/tandem mass spectrometry[J]. APMIS, 2016,124(11):1004-1015.