Examination of Quinidine and Quinine and Their Pharmaceutical Preparations

Smith, Edward C.; Barkan, Susan; Ross, Bruce S.; Maienthal, Millard; Levine, Joseph

doi:10.1002/jps.2600620720

Cited by 40 publications

(8 citation statements)

References 12 publications

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“…(5) mp 169 and 174'1; Rf 0.1 (chloroformethyl acetate, 2:l). Pure I1 was obtained by a repetition of the chromatographic procedure.…”

Section: I1mentioning

confidence: 99%

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NMR Spectroscopic Determination of Preferred Conformations of Quinidine and Hydroquinidine

Yanuka

Superstine

1979

Journal of Pharmaceutical Sciences

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“…(5) mp 169 and 174'1; Rf 0.1 (chloroformethyl acetate, 2:l). Pure I1 was obtained by a repetition of the chromatographic procedure.…”

Section: I1mentioning

confidence: 99%

“…Therefore, it is not surprising that different investigators have reported varying data concerning the chemical shift of this OH proton (5). Therefore, it is not surprising that different investigators have reported varying data concerning the chemical shift of this OH proton (5).…”

Section: I1mentioning

confidence: 99%

NMR Spectroscopic Determination of Preferred Conformations of Quinidine and Hydroquinidine

Yanuka

Superstine

1979

Journal of Pharmaceutical Sciences

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“…Dihydroquinidine (DQ) is present as an impurity in variable amounts in quinidine preparations (Huynh-Ngoc and Sirois, 1974;Smith et al, 1973). The fact that it is structurally related to quinidine, led in the past to its being considered as one of the many quinidine salts employed as antiarrhythmic agents; however experimental and clinical studies (Hailey et 1945;Ueda and Makoid, 1979;Ueda et al, 1976;Weisman, 1942) have shown that the kinetics and bioavailability of DQ differ from those of quinidine; some other observations (Balazs et al, 1978;Dietman et al, 1977;Hollander and Besch, 1969) suggest that DQ has a different electrophysiologic action and that in some experimental settings DQ may be even more effective than quinidine (Alexander et Unlike quinidine, which is still widely used worldwide, purified DQ is commercially available in only a few countries.…”

Section: Introductionmentioning

confidence: 99%

Dihydroquinidine versus disopyramide: Efficacy in patients with chronic stable ventricular ectopy

Chimienti

Panciroli

et al. 1984

Clinical Cardiology

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Summary: Dihydroquinidine (DQ) is contained in sub-stantial amounts in quinidine salts, but its direct antiarrhythmic action has not been studied. The efficacy of oral DQ (300 mg t.i.d.) compared to disopyramide (D) (200 mg t.i.d.) was thus investigated using a double-blind crossover placebo-controlled protocol in 12 patients, aged 13 to 67 years, with chronic stable high frequency premature ventricular beats (PVB), defined as > 100 PVB/h during 48-72-h control Holter monitoring. The protocol included three 72-h treatment periods: DQ, D, and placebo at random. On days 2 and 3 of each period a 24-h Holter recording was carried out; drug blood levels were determined at peak (days 2 and 3) and trough time (day 3). No significant difference in the mean PVB/h was found between control (735 +400) and placebo periods complex PVBs were abolished in 3 of 6 patients on both treatments. On day 3, DQ plasma levels were 1.3 1 f0.44 (peak) and 0.92f0.45 (trough) mg/l; D plasma levels were 2.88Ik0.64 (peak) and 2.02Ik0.31 (trough) mg/l; no significant difference was found between day 2 and day 3 samples. Side effects were cutaneous rashes in one patient on DQ and pyrosis in one patient on D. The conclusion is that DQ at the doses used is a very effective and well-tolerated antiarrhythmic agent. In this study it appeared to be superior to average doses of D for suppressing chronic ventricular arrhythmias.

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“…Numerous chromatographic procedures have been developed for the determination of quinidine (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). Several of them (7-10) are specific but time-consuming TLC procedures which we did not consider suitable for routine clinical monitoring.…”

mentioning

confidence: 99%

“…Several of them (7-10) are specific but time-consuming TLC procedures which we did not consider suitable for routine clinical monitoring. Some of them (11,12) have been applied only to pharmaceutical preparations. Several others (13)(14)(15) did not separate quinidine from dihydroquinidine.…”

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confidence: 99%

Determination of quinidine and dihydroquinidine in plasma by high performance liquid chromatography

Kline¹,

Turner²,

Barr³

1979

Anal. Chem.

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A rapid, specific and sensitive high performance liquid chromatographic method has been developed for the determination of quinidine (Q) and dihydroquinidine (DHQ) in human plasma. Plasma samples are extracted with a benzene-isoamyl alcohol mixture ( 1: 1) followed by separation on a microparticulate reverse-phase column. Quinidine, dihydroquinidine, and their metabolltes are detected by fluorescence In acid medlum using post-column additlon of sulfuric acid. Plasma concentrations as low as 0.05 pg/mL can be measured with a relative standard deviation less than 10%. The complete assay procedure takes about 30 min.Recovery from plasma is at least 95 YO. A linear response is obtained in the concentration range of 0.05 to 10 pg/mL of quinidine in plasma. The minimum detectable quantity is 1 ng on column.To study quinidine pharmacokinetics in human subjects, a specific method for the separation and determination of quinidine, dihydroquinidine, and their metabolites is needed. Quinidine may contain u p to 20% of a natural contaminant, dihydroquinidine, depending on the source ( I ) . Dihydroquinidine is an analogue of quinidine with similar if not greater antiarrhythmic effect ( 2 , 3 ) . Drayer et al. have reported that three metabolites of quinidine found in man are pharmacologically active in mice and rabbits ( 4 ) . Until this activity, or lack thereof, is verified in humans, plasma level determinations of quinidine for the purpose of therapeutic dosage adjustment should be specific with minimal contribution from dihydroquinidine or metabolites. The analytical method commonly used to determine quinidine in plasma is that of Cramer and Isaksson (5). This method is based on extraction of alkalinized plasma samples with benzene, which excludes the more polar metabolites, and then back extraction into H2S04 for fluorimetric quantitation of t h e quinidine.However, Huynh-Ngoc and Sirios (6) have found t h a t some metabolites are being measured along with the quinidine in this method. They recommend washing the benzene layer with NaOH to eliminate interferences from less polar metabolites.Numerous chromatographic procedures have been developed for the determination of quinidine (7-19). Several of them (7-10) are specific but time-consuming TLC procedures which we did not consider suitable for routine clinical monitoring. Some of them (11, 12) have been applied only to pharmaceutical preparations. Several others (13-15) did not separate quinidine from dihydroquinidine. The method presented here provides good separation of quinidine, dihydroquinidine, and their metabolites, is sensitive enough to determine low concentrations of quinidine and dihydroquinidine, and is rapid enough for routine clinical monitoring of plasma levels. EXPERIMENTALApparatus. A Waters Model ALC202 liquid chromatograph fitted with a Model 6000 constant flow pump, a 30 cm X 3.9 mm i.d. pBondapak C18 column (Waters Associates, Milford, Mass.) and a Rheodyne Model 7120 syringe loading sample injector with a 175-pL sample loop was used. A 5 cm X 2 mm ...

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Examination of Quinidine and Quinine and Their Pharmaceutical Preparations

Cited by 40 publications

References 12 publications

NMR Spectroscopic Determination of Preferred Conformations of Quinidine and Hydroquinidine

NMR Spectroscopic Determination of Preferred Conformations of Quinidine and Hydroquinidine

Dihydroquinidine versus disopyramide: Efficacy in patients with chronic stable ventricular ectopy

Determination of quinidine and dihydroquinidine in plasma by high performance liquid chromatography

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